{"@context":"https://schema.org","@type":"Dataset","name":"LYO Research evidence grades for peptides","description":"Evidence-graded outcomes for peptides, human studies only, with references. Grades: A established, B probable, C weak, D no human evidence.","url":"https://lyoresearch.com/api/v1/compounds","license":"https://creativecommons.org/licenses/by/4.0/","creator":{"@type":"Organization","name":"LYO Research","url":"https://lyoresearch.com"},"dateModified":"2026-10-07","version":"2026-10-07","count":76,"compounds":[{"id":"bpc-157","name":"BPC-157","aliases":["Body Protection Compound 157","BPC157","Bepecin"],"url":"https://lyoresearch.com/compounds/bpc-157","class":{"id":"healing-peptides","name":"Tissue-repair peptides","url":"https://lyoresearch.com/classes/healing-peptides"},"summary":"BPC-157 is a synthetic 15-amino-acid peptide derived from a protein found in human gastric juice. In rodents it consistently speeds healing of tendon, ligament, muscle and gut injury. In people it has never been tested in a controlled trial, so every human claim about it — healing, pain relief, safety — is currently unproven. It is not an approved medicine anywhere and is prohibited in sport.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 controlled","regulatory_status":"Not approved","molecule":{"formula":"C62H98N16O22","molecular_weight":"1419.5","cas":"137525-51-0","pubchem_cid":9941957,"note":null},"pharmacokinetics":{"basis":"animal","route":"Injected or oral as sold; no human study of either","half_life":"No human data. In rats and dogs the intravenous half-life was 5–15 minutes","licensed_regimen":null,"product":null,"source":{"title":"He L, et al. Pharmacokinetics, distribution, metabolism, and excretion of body-protective compound 157 in rats and dogs. Front Pharmacol 2022","url":"https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.1026182/full"}},"outcomes":[{"outcome":"Tendon & ligament healing","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Rodent models of Achilles and MCL injury. Consistent in animals; no human trial has been run.","references":[{"citation":"Sikiric P, et al. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.","where":"Curr Pharm Des, 2011 (review)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sikiric+BPC+157+gastrointestinal+review+2011"},{"citation":"Chang CH, et al. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration.","where":"J Appl Physiol, 2011","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Chang+BPC+157+tendon+healing+2011"}]},{"outcome":"Gut mucosal healing","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Rat ulcer and colitis models. The original research programme; still preclinical.","references":[{"citation":"Sikiric P, et al. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.","where":"Curr Pharm Des, 2011 (review)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sikiric+BPC+157+gastrointestinal+review+2011"}]},{"outcome":"Pain reduction","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 case series (n=12)","evidence":"A retrospective case report of 12 knee-pain patients given intra-articular injections; no control group. The only human study a 2025 systematic review could find.","references":[{"citation":"Vasireddi N, Hahamyan H, Salata MJ, et al. Emerging use of BPC-157 in orthopaedic sports medicine: a systematic review.","where":"HSS Journal, 2025;21(4):485–495","url":"https://doi.org/10.1177/15563316251355551"}]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"1 open-label pilot (n=2)","evidence":"Two healthy adults given intravenous doses in an uncontrolled 2025 pilot showed no biomarker changes. That is the entire human safety literature.","references":[{"citation":"Vasireddi N, Hahamyan H, Salata MJ, et al. Emerging use of BPC-157 in orthopaedic sports medicine: a systematic review.","where":"HSS Journal, 2025;21(4):485–495","url":"https://doi.org/10.1177/15563316251355551"},{"citation":"Lee E, Burgess J. Intravenous BPC-157 in healthy adults: an open-label pilot.","where":"2025 (pilot, n = 2)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=BPC+157+intravenous+pilot+healthy+adults+2025"},{"citation":"U.S. FDA. Certain bulk drug substances for use in compounding that may present significant safety risks (BPC-157).","where":"FDA, 2023","url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks"}]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; 'research use only' labels do not change that."},{"region":"United States","status":"Not approved; compounding under review","note":"Removed from FDA's Category 2 list on 22 April 2026; the Pharmacy Compounding Advisory Committee recommended it for the 503A bulks list in July 2026 (8–6, 1 abstention). Not on the list yet and not an approved drug. Sold otherwise as an unapproved 'research chemical'."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it is an offence under the Human Medicines Regulations 2012; importing a small quantity purely for personal use is not itself an offence, but consignments are seized."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG. Obtainable only on prescription (compounded or imported under the Personal Importation Scheme with a prescription). Named in the TGA's April 2026 advisory."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it is illegal. Among the products Health Canada seized from a domestic vendor in August 2025. Residents cannot import prescription drugs by mail."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Named under S0 (non-approved substances) on the Prohibited List since 2022."}],"faq":[{"q":"Is there any human research on BPC-157?","a":"No controlled trials. A 2025 systematic review screened 544 articles from 1993–2024 and found one human study — a retrospective case report of 12 patients — alongside 35 animal studies. A separate 2025 pilot gave the peptide intravenously to two healthy volunteers without a control group. Neither design can show that the peptide caused an effect."},{"q":"Why is the grade D if the animal results are so consistent?","a":"Because LYO grades only count human evidence. Consistent animal data is exactly the reason a human trial should be run — it is not a reason to grade as though one had been."},{"q":"Is BPC-157 safe?","a":"Unknown. No systematic safety data exists in humans. A lack of reported harm in a market with no reporting system is not evidence of safety."},{"q":"Is BPC-157 legal?","a":"It is not an approved medicine in any major market. In the EU, selling it for human use is an offence for the seller. It is prohibited in sport by WADA. Rules for possession vary by country."}],"references":[{"cite":"Sikiric P, et al. Stable gastric pentadecapeptide BPC 157: novel therapy in gastrointestinal tract.","where":"Curr Pharm Des, 2011 (review)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sikiric+BPC+157+gastrointestinal+review+2011","note":"Animal data; the originating laboratory."},{"cite":"Chang CH, et al. The promoting effect of pentadecapeptide BPC 157 on tendon healing involves tendon outgrowth, cell survival, and cell migration.","where":"J Appl Physiol, 2011","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Chang+BPC+157+tendon+healing+2011","note":"Rat Achilles tendon model."},{"cite":"Vasireddi N, Hahamyan H, Salata MJ, et al. Emerging use of BPC-157 in orthopaedic sports medicine: a systematic review.","where":"HSS Journal, 2025;21(4):485–495","url":"https://doi.org/10.1177/15563316251355551","note":"544 articles screened; 36 included — 35 preclinical, 1 clinical (a 12-patient retrospective case report). No clinical safety data found."},{"cite":"Lee E, Burgess J. Intravenous BPC-157 in healthy adults: an open-label pilot.","where":"2025 (pilot, n = 2)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=BPC+157+intravenous+pilot+healthy+adults+2025","note":"Uncontrolled; biomarkers only; no efficacy endpoints. Same research group as other human reports."},{"cite":"U.S. FDA. Certain bulk drug substances for use in compounding that may present significant safety risks (BPC-157).","where":"FDA, 2023","url":"https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks","note":"Regulatory status in the United States."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Human-evidence rows made precise: one retrospective case series (n=12) and one open-label IV pilot (n=2) now cited; 2025 systematic review added. Grades unchanged."},{"date":"2026-09-01","note":"Initial publication. All outcomes graded D on the basis of no controlled human trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"semaglutide","name":"Semaglutide","aliases":["Ozempic","Wegovy","Rybelsus","GLP-1 receptor agonist"],"url":"https://lyoresearch.com/compounds/semaglutide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Semaglutide is a once-weekly GLP-1 receptor agonist approved for type 2 diabetes and, at a higher dose, for weight management. In large randomised trials it produces roughly 15% average weight loss over 68 weeks and reduces major cardiovascular events in people with existing heart disease. Gastrointestinal side effects are common and are the main reason people stop. It is a prescription medicine; products sold outside that channel are unlicensed copies.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"30+ RCTs","regulatory_status":"Approved (Rx)","molecule":{"formula":"C187H291N45O59","molecular_weight":"4114","cas":"910463-68-2","pubchem_cid":56843331,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, once weekly (also oral tablet, once daily)","half_life":"About 1 week","licensed_regimen":"Injection: 0.25 mg weekly for 4 weeks, then 0.5 mg (weeks 5-8), 1 mg (weeks 9-12), 1.7 mg (weeks 13-16); maintenance 2.4 mg weekly, up to 7.2 mg weekly for additional weight reduction in adults. Tablets: 1.5 mg daily for 30 days, then 4 mg (days 31-60), 9 mg (days 61-90); maintenance 25 mg daily","product":"Wegovy","source":{"title":"Wegovy prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b"}},"outcomes":[{"outcome":"Body weight","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"15+ RCTs","evidence":"STEP programme. Roughly 15% mean loss at 68 weeks versus placebo; consistent across trials.","references":[{"citation":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/33567185/"}],"verbatim":{"text":"The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001).","citation":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","url":"https://pubmed.ncbi.nlm.nih.gov/33567185/"}},{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"10+ RCTs","evidence":"SUSTAIN programme; the original approval basis in type 2 diabetes.","references":[{"citation":"Sorli C, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in type 2 diabetes (SUSTAIN 1).","where":"Lancet Diabetes Endocrinol, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/28110911/"}],"verbatim":{"text":"Mean baseline HbA1c was 8·05% (SD 0·85); at week 30, HbA1c significantly decreased by 1·45% (95% CI -1·65 to -1·26) with 0·5 mg semaglutide (estimated treatment difference vs placebo -1·43%, 95% CI -1·71 to -1·15; p<0·0001), significantly decreased by 1·55% (-1·74 to -1·36) with 1·0 mg semaglutide (estimated treatment difference vs placebo -1·53%, -1·81 to -1·25; p<0·0001), and non-significantly decreased by 0·02% (-0·23 to 0·18) with placebo.","citation":"Sorli C, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in type 2 diabetes (SUSTAIN 1).","url":"https://pubmed.ncbi.nlm.nih.gov/28110911/"}},{"outcome":"Major cardiovascular events","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"1 large RCT","evidence":"SELECT trial, 17,604 participants: a 20% relative reduction in people with established cardiovascular disease and no diabetes. A mediation analysis of the trial, published in September 2026, estimated that the measured changes in weight, waist, blood sugar, lipids, blood pressure, inflammation and kidney markers together explain about a third of that reduction (31.4%), with a confidence interval from −30.1% to 143.6% — too wide to say how the drug protects the heart.","references":[{"citation":"Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).","where":"N Engl J Med, 2023;389:2221–2232","url":"https://pubmed.ncbi.nlm.nih.gov/37952131/"},{"citation":"Colhoun HM, et al. Semaglutide and cardiovascular risk reduction: a mediation analysis of the SELECT trial.","where":"Eur Heart J, 2026 (online Sep 2026)","url":"https://pubmed.ncbi.nlm.nih.gov/42777687/"}],"verbatim":{"text":"A primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001).","citation":"Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).","url":"https://pubmed.ncbi.nlm.nih.gov/37952131/"}},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"All trials","evidence":"Nausea, vomiting and constipation are the most common reasons people stop. Well quantified.","references":[{"citation":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/33567185/"},{"citation":"Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).","where":"N Engl J Med, 2023;389:2221–2232","url":"https://pubmed.ncbi.nlm.nih.gov/37952131/"}],"verbatim":{"text":"Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time.","citation":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","url":"https://pubmed.ncbi.nlm.nih.gov/33567185/"}},{"outcome":"Lean mass loss","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":true,"human_studies":"Sub-studies","evidence":"A share of weight lost is lean tissue; magnitude and clinical importance still debated.","references":[{"citation":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/33567185/"},{"citation":"Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension.","where":"Diabetes Obes Metab, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+extension+withdrawal+semaglutide+2022"}]},{"outcome":"BMI in children aged 6–11","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT topline (n=165)","evidence":"STEP Young, reported by press release on 7 September 2026: the primary BMI endpoint was met at 68 weeks, and 40.4% of children on semaglutide finished below the obesity threshold against 0% on placebo. Novo Nordisk reports no growth or pubertal safety signal. Graded B until the paper appears; full data promised for November 2026.","references":[{"citation":"Novo Nordisk. STEP Young phase 3 trial of semaglutide in children aged 6 to under 12 with obesity: topline results.","where":"Press release, 7 Sep 2026","url":"https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916600"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Ozempic (2018) and Wegovy (2022) authorised via the EMA. Grey-market vials and pens are unlicensed medicines."},{"region":"United States","status":"Approved, prescription-only","note":"Ozempic, Wegovy and Rybelsus. Compounded copies were tolerated only during the shortage, which the FDA declared resolved in February 2025; enforcement discretion ended 22 April (503A) and 22 May 2025 (503B). 990 adverse-event reports for compounded versions by May 2026."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Ozempic, Wegovy and Rybelsus licensed by the MHRA; available on prescription including from registered online pharmacies. Anything sold without a prescription is unlicensed."},{"region":"Australia","status":"Registered, Schedule 4","note":"Ozempic and Wegovy on the ARTG, prescription-only. Compounded semaglutide has been unlawful since the TGA ended the GLP-1 compounding exemption on 1 October 2024."},{"region":"Canada","status":"Authorised, prescription-only","note":"Ozempic and Wegovy carry a DIN. Vials sold online as semaglutide were among the products Health Canada seized in August 2025. One lot of a generic semaglutide pen was recalled in September 2026 because it could display and deliver a lower dose than expected."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the 2026 Prohibited List, and WADA confirmed on 21 September 2026 that GLP-1 receptor agonists stay off the 2027 List. Semaglutide remains on WADA's Monitoring Program."}],"faq":[{"q":"How much weight do people lose on semaglutide?","a":"In the STEP 1 trial, adults without diabetes lost about 15% of body weight on average over 68 weeks, compared with about 2.4% on placebo. Individual results vary widely."},{"q":"Does the weight come back after stopping?","a":"Largely, yes. In the trial that withdrew treatment after a year, participants regained about two-thirds of the lost weight within the following year."},{"q":"Is semaglutide a peptide?","a":"Yes — it is a 31-amino-acid peptide, a modified form of the natural hormone GLP-1."},{"q":"Why are there so many fake versions?","a":"Demand outstripped supply for several years, and the molecule is relatively simple to synthesise. Products sold outside the prescription channel are unlicensed and, in enforcement seizures, frequently underdosed or misidentified."}],"references":[{"cite":"Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1).","where":"N Engl J Med, 2021;384:989–1002","url":"https://pubmed.ncbi.nlm.nih.gov/33567185/","note":"1,961 adults; −14.9% vs −2.4% at 68 weeks."},{"cite":"Sorli C, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in type 2 diabetes (SUSTAIN 1).","where":"Lancet Diabetes Endocrinol, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/28110911/","note":"First of the SUSTAIN programme."},{"cite":"Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).","where":"N Engl J Med, 2023;389:2221–2232","url":"https://pubmed.ncbi.nlm.nih.gov/37952131/","note":"17,604 participants; hazard ratio 0.80 for MACE."},{"cite":"Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension.","where":"Diabetes Obes Metab, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Wilding+STEP+1+extension+withdrawal+semaglutide+2022","note":"Two-thirds of lost weight regained within a year of stopping."},{"cite":"Novo Nordisk. STEP Young phase 3 trial of semaglutide in children aged 6 to under 12 with obesity: topline results.","where":"Press release, 7 Sep 2026","url":"https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916600","note":"165 children, 68 weeks. Topline; not peer-reviewed. Full results due at ObesityWeek, 14–17 Nov 2026."},{"cite":"Colhoun HM, et al. Semaglutide and cardiovascular risk reduction: a mediation analysis of the SELECT trial.","where":"Eur Heart J, 2026 (online Sep 2026)","url":"https://pubmed.ncbi.nlm.nih.gov/42777687/","note":"Joint mediation by all measured risk factors 31.4% (95% CI −30.1 to 143.6); the authors conclude the effect cannot be fully ascribed to known risk factors."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"SELECT mediation analysis (Eur Heart J, Sep 2026) added to the cardiovascular row; WADA's 2027 List status (published 21 Sep 2026) and a Canadian recall of one generic lot added to the regional rows. Grades unchanged."},{"date":"2026-09-23","note":"New row for the STEP Young paediatric trial (topline, 7 Sep 2026), graded B pending publication. Overall grade unchanged."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"retatrutide","name":"Retatrutide","aliases":["LY3437943","triple agonist","GIP/GLP-1/glucagon agonist"],"url":"https://lyoresearch.com/compounds/retatrutide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Retatrutide is an investigational once-weekly peptide that activates three receptors at once: GIP, GLP-1 and glucagon. In TRIUMPH-1, a 2,339-person phase 3 trial published in September 2026, adults with obesity lost 25.0% of body weight at 80 weeks on the top dose against 3.9% on placebo; in adults who also have type 2 diabetes the figure was 18.8% (TRIUMPH-2). A separate published trial cut HbA1c by up to 1.9 percentage points. It is not approved anywhere, and no legitimate supply exists outside clinical trials.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"3 phase 3 RCTs published (n=2,339; n=1,152; n=537); 2 phase 3 topline","regulatory_status":"Investigational","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"No PubChem Compound record at review (investigational; LY3437943)"},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, once weekly","half_life":"About 6 days (phase 1b)","licensed_regimen":null,"product":null,"source":{"title":"Urva S, et al. LY3437943, a novel triple GIP, GLP-1 and glucagon receptor agonist in people with type 2 diabetes: a phase 1b multiple-ascending-dose trial. Lancet 2022","url":"https://pubmed.ncbi.nlm.nih.gov/36354040/"}},"outcomes":[{"outcome":"Body weight","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"2 phase 3 + 1 phase 2 RCT published; 2 phase 3 topline","evidence":"TRIUMPH-1, published in the New England Journal of Medicine on 29 September 2026 (2,339 adults with obesity and no diabetes, 80 weeks): −17.6% on 4 mg, −23.7% on 9 mg and −25.0% on 12 mg versus −3.9% on placebo. TRIUMPH-2, published in The Lancet the same day (1,152 adults with obesity and type 2 diabetes, 80 weeks): −11.9%, −16.8% and −18.8% versus −5.1%. Both papers count every participant randomised; the figures first announced by press release, 28.3% and 20.8% on 12 mg, were higher. Phase 2: −24.2% at 48 weeks on 12 mg. Still press releases only: TRIUMPH-4 (−28.7% at 68 weeks vs −2.1% placebo), TRIUMPH-3 (1,949 adults with severe obesity and cardiovascular disease: −22.6% vs −3.2%) and the 104-week TRIUMPH-1 extension in people with a BMI of 35 or more (−30.3%).","references":[{"citation":"Jastreboff AM, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1).","where":"N Engl J Med, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42814954/"},{"citation":"Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial.","where":"Lancet, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42810372/"},{"citation":"Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial.","where":"N Engl J Med, 2023;389:514–526","url":"https://pubmed.ncbi.nlm.nih.gov/37366315/"},{"citation":"Eli Lilly. Retatrutide delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial (TRIUMPH-4).","where":"Press release, 11 Dec 2025","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average"},{"citation":"Eli Lilly. Retatrutide TRIUMPH-1 topline results (NCT05929066).","where":"Press release, May 2026","url":"https://www.ajmc.com/view/retatrutide-achieves-up-to-30-3-average-weight-loss-in-phase-3-triumph-1-trial"},{"citation":"Eli Lilly. Lilly's triple agonist retatrutide successful in two additional phase 3 obesity trials (TRIUMPH-2, TRIUMPH-3).","where":"Press release, 23 Jul 2026","url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html"}],"verbatim":{"text":"The mean percent change in body weight in the retatrutide groups was -17.6% (4-mg dose), -23.7% (9-mg dose), and -25.0% (12-mg dose) versus -3.9% in the placebo group (differences, -19.8 and -21.0 percentage points, respectively; P<0.001 for both comparisons).","citation":"Jastreboff AM, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1).","url":"https://pubmed.ncbi.nlm.nih.gov/42814954/"}},{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"1 phase 3 + 1 phase 2 RCT","evidence":"TRANSCEND-T2D-1, a published 40-week phase 3 trial in 537 adults with type 2 diabetes uncontrolled by diet and exercise: HbA1c fell 1.69–1.94 percentage points across doses versus 0.81 on placebo. The earlier phase 2 trial agreed.","references":[{"citation":"Bajaj HS, et al. Efficacy and safety of retatrutide in people with type 2 diabetes inadequately controlled with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.","where":"Lancet, 2026;407:2402–2413","url":"https://pubmed.ncbi.nlm.nih.gov/42250575/"},{"citation":"Rosenstock J, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, phase 2 trial.","where":"Lancet, 2023;402:529–544","url":"https://pubmed.ncbi.nlm.nih.gov/37385280/"}],"verbatim":{"text":"For the treatment regimen estimand, the mean change from baseline in HbA1c concentration was -1·69% (SE 0·11) with retatrutide 4 mg, -1·86% (0·10) with 9 mg, and -1·94% (0·08) with 12 mg, versus -0·81% (0·12) with placebo, resulting in estimated treatment differences versus placebo of -0·88% (95% CI -1·18 to -0·59) with retatrutide 4 mg, -1·04% (-1·32 to -0·76) with 9 mg, and -1·12% (-1·39 to -0·85) with 12 mg (all p<0·0001).","citation":"Bajaj HS, et al. Efficacy and safety of retatrutide in people with type 2 diabetes inadequately controlled with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/42250575/"}},{"outcome":"Knee osteoarthritis pain","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT published (subgroup n=574); 1 phase 3 topline","evidence":"TRIUMPH-1, now published, included 574 participants with knee osteoarthritis: WOMAC pain fell 3.9 points on 9 mg and 4.1 on 12 mg versus 2.5 on placebo, counting everyone randomised (differences −1.4 and −1.6; both P<0.001). TRIUMPH-4, still a press release, enrolled only adults with obesity and knee osteoarthritis: up to 4.5 points (75.8%) vs 2.4 (40.3%) on placebo. Weight loss likely explains much of it.","references":[{"citation":"Jastreboff AM, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1).","where":"N Engl J Med, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42814954/"},{"citation":"Eli Lilly. Retatrutide delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial (TRIUMPH-4).","where":"Press release, 11 Dec 2025","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average"}],"verbatim":{"text":"Among the participants with knee osteoarthritis, the corresponding changes in the pain score in the retatrutide groups for the hybrid estimand were -3.2, -3.5, and -3.6 versus -1.9 with placebo (differences, -1.6 and -1.8 points; both P<0.001); the corresponding changes for the ITT estimand were -3.4, -3.9, and -4.1 versus -2.5 with placebo (differences, -1.4 and -1.6 points; both P<0.001).","citation":"Jastreboff AM, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1).","url":"https://pubmed.ncbi.nlm.nih.gov/42814954/"}},{"outcome":"Obstructive sleep apnoea","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT (subgroup n=243)","evidence":"In the 243 TRIUMPH-1 participants with obstructive sleep apnoea, the apnoea–hypopnoea index fell by 34.3 events per hour on 9 mg and 32.1 on 12 mg versus 9.6 on placebo at 80 weeks, counting everyone randomised (differences −24.7 and −22.5; both P<0.001). One subgroup of one trial, so B. The sleep-apnoea results from TRIUMPH-2 have not been reported yet.","references":[{"citation":"Jastreboff AM, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1).","where":"N Engl J Med, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42814954/"}]},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"2 phase 3 + 1 phase 2 RCT published; phase 3 topline","evidence":"TRIUMPH-2, published: diarrhoea in 27–34% vs 13% on placebo and nausea in 14–28% vs 8%; 12% on 9 mg and 8% on 12 mg stopped treatment because of adverse events or death, against 5% on placebo. TRIUMPH-1, published, also names gastrointestinal events as the most common. Press releases: TRIUMPH-4, nausea 38–43% vs 11%, vomiting 20–21% vs 0%, discontinuation for adverse events 12–18% vs 4%; TRIUMPH-1, 11.3% stopped on 12 mg vs 4.9% placebo; TRIUMPH-3, 13.5% vs 4.8%.","references":[{"citation":"Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial.","where":"Lancet, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42810372/"},{"citation":"Jastreboff AM, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1).","where":"N Engl J Med, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42814954/"},{"citation":"Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial.","where":"N Engl J Med, 2023;389:514–526","url":"https://pubmed.ncbi.nlm.nih.gov/37366315/"},{"citation":"Eli Lilly. Retatrutide delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial (TRIUMPH-4).","where":"Press release, 11 Dec 2025","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average"},{"citation":"Eli Lilly. Retatrutide TRIUMPH-1 topline results (NCT05929066).","where":"Press release, May 2026","url":"https://www.ajmc.com/view/retatrutide-achieves-up-to-30-3-average-weight-loss-in-phase-3-triumph-1-trial"},{"citation":"Eli Lilly. Lilly's triple agonist retatrutide successful in two additional phase 3 obesity trials (TRIUMPH-2, TRIUMPH-3).","where":"Press release, 23 Jul 2026","url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html"}],"verbatim":{"text":"The most common adverse events in the retatrutide groups were gastrointestinal; these events were dose-related, were mostly mild to moderate in severity, and were partially mitigated with a lower starting dose (2 mg vs. 4 mg).","citation":"Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/37366315/"}},{"outcome":"Dysesthesia (skin sensation changes)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"1 phase 3 RCT published; phase 3 topline","evidence":"TRIUMPH-2, published: dysesthesia in 4%, 6% and 7% on 4, 9 and 12 mg versus 1% on placebo; hypotension was also more frequent (1%, 5% and 6% vs under 1%). Press releases: 9–21% of treated participants vs 0.7% on placebo in TRIUMPH-4, and 4.5–7.3% vs 0.7–1.3% in TRIUMPH-2 and -3 — an effect not prominent with older GLP-1 drugs.","references":[{"citation":"Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial.","where":"Lancet, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42810372/"},{"citation":"Eli Lilly. Retatrutide delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial (TRIUMPH-4).","where":"Press release, 11 Dec 2025","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average"},{"citation":"Eli Lilly. Lilly's triple agonist retatrutide successful in two additional phase 3 obesity trials (TRIUMPH-2, TRIUMPH-3).","where":"Press release, 23 Jul 2026","url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html"}],"verbatim":{"text":"Hypotension and dysesthesia were more frequent with retatrutide than with placebo (four [1%] in the 4 mg group, 14 [5%] in the 9 mg group, and 18 (6%) in the 12 mg group vs one [<1%] in the placebo group with hypotension; 13 [4%], 16 [6%], and 21 [7%] vs two [1%] in the placebo group with dysesthesia).","citation":"Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/42810372/"}}],"regions":[{"region":"European Union","status":"Investigational; not authorised","note":"No marketing authorisation anywhere; supply outside clinical trials is unlawful. Unlicensed pens were among the seizures in Europol's 2025 operation."},{"region":"United States","status":"Investigational; cannot be compounded","note":"FDA: retatrutide 'cannot be used in compounding under federal law' and has not been found safe and effective for any condition. Lilly has said it plans to file for approval in the first quarter of 2027."},{"region":"United Kingdom","status":"Unlicensed; illegal to sell","note":"MHRA, July 2026: 'it has not been authorised for use in the UK, meaning anyone selling this product is doing so illegally.' Thousands of doses seized in raids in October 2025, February and May 2026."},{"region":"Australia","status":"Unapproved","note":"Not registered anywhere. Named in the TGA's April 2026 advisory on unapproved peptide products."},{"region":"Canada","status":"Not authorised","note":"Investigational. Among the products Health Canada seized from a domestic vendor in August 2025."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so it falls under S0 (non-approved substances)."}],"faq":[{"q":"How much weight do people lose on retatrutide?","a":"In TRIUMPH-1, published in September 2026, adults with obesity and no diabetes lost 25.0% of body weight on average over 80 weeks on the 12 mg dose, against 3.9% on placebo. Adults who also have type 2 diabetes lost 18.8% in TRIUMPH-2. In phase 2 the figure was 24.2% at 48 weeks. These are averages across everyone randomised; individual results vary widely."},{"q":"Is retatrutide better than tirzepatide?","a":"Probably more weight loss, on the numbers so far — but no trial has compared them head-to-head, and cross-trial comparisons are unreliable. The side-effect burden also appears higher. Treat “better” as unsettled until a direct comparison exists."},{"q":"Is retatrutide available?","a":"Not legally, anywhere. It is an investigational medicine available only in clinical trials. Products sold online under the name are unlicensed and, in enforcement seizures, frequently not what the label says."},{"q":"Why is the overall grade B and not A?","a":"Body weight moved to A on 7 October 2026, once two phase 3 obesity trials had been published in peer-reviewed journals. The overall grade stays B because retatrutide is not approved anywhere, two further phase 3 trials exist only as press releases, and no cardiovascular outcomes trial has reported."}],"references":[{"cite":"Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial.","where":"N Engl J Med, 2023;389:514–526","url":"https://pubmed.ncbi.nlm.nih.gov/37366315/","note":"338 adults; −24.2% at 48 weeks on 12 mg."},{"cite":"Eli Lilly. Retatrutide delivered weight loss of up to an average of 71.2 lbs along with substantial relief from osteoarthritis pain in first successful phase 3 trial (TRIUMPH-4).","where":"Press release, 11 Dec 2025","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-weight-loss-average","note":"445 adults, 68 weeks. Topline; not peer-reviewed."},{"cite":"Eli Lilly. Retatrutide TRIUMPH-1 topline results (NCT05929066).","where":"Press release, May 2026","url":"https://www.ajmc.com/view/retatrutide-achieves-up-to-30-3-average-weight-loss-in-phase-3-triumph-1-trial","note":"2,339 adults, 80 weeks plus 104-week extension. Detailed data promised for the ADA Scientific Sessions; not peer-reviewed at time of review."},{"cite":"Bajaj HS, et al. Efficacy and safety of retatrutide in people with type 2 diabetes inadequately controlled with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial.","where":"Lancet, 2026;407:2402–2413","url":"https://pubmed.ncbi.nlm.nih.gov/42250575/","note":"537 randomised, 40 weeks. The first published phase 3 trial of retatrutide."},{"cite":"Rosenstock J, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, phase 2 trial.","where":"Lancet, 2023;402:529–544","url":"https://pubmed.ncbi.nlm.nih.gov/37385280/","note":"Phase 2 in type 2 diabetes; agrees with the phase 3 on glycaemic effect."},{"cite":"Eli Lilly. Lilly's triple agonist retatrutide successful in two additional phase 3 obesity trials (TRIUMPH-2, TRIUMPH-3).","where":"Press release, 23 Jul 2026","url":"https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html","note":"TRIUMPH-2: 1,152 adults with obesity and type 2 diabetes, 80 weeks. TRIUMPH-3: 1,949 adults with severe obesity and cardiovascular disease, 80 weeks. Topline; not peer-reviewed. Lilly intends to file with the FDA in Q1 2027."},{"cite":"Jastreboff AM, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1).","where":"N Engl J Med, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42814954/","note":"2,339 randomised, 80 weeks; −25.0% on 12 mg vs −3.9% placebo by intention to treat. Subgroups with knee osteoarthritis (n=574) and obstructive sleep apnoea (n=243). NCT05929066."},{"cite":"Bellido V, et al. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial.","where":"Lancet, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42810372/","note":"1,152 randomised, 92 sites, 80 weeks; −18.8% on 12 mg vs −5.1% placebo (treatment-regimen estimand). NCT05929079."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"TRIUMPH-1 (N Engl J Med) and TRIUMPH-2 (Lancet) were published on 29 Sep 2026. Body weight and GI side effects move from B to A on the published papers, with the intention-to-treat figures (25.0% and 18.8%) replacing the press-release ones; knee-pain and dysesthesia rows now cite the papers; new sleep-apnoea row at B. Overall grade held at B: unapproved, TRIUMPH-3 and -4 unpublished."},{"date":"2026-09-23","note":"TRIUMPH-2 and TRIUMPH-3 topline results (23 Jul 2026) added to the weight, side-effect and dysesthesia rows. Still press releases, so body weight stays at B."},{"date":"2026-09-03","note":"TRANSCEND-T2D-1, the first published phase 3 trial of retatrutide (Lancet, 537 adults with type 2 diabetes), added with a verbatim primary result; new blood-glucose row graded A. The obesity phase 3 results remain unpublished press releases, so body weight stays at B."},{"date":"2026-09-02","note":"Full page: mechanism, regulatory status and FAQ added. Phase 3 topline results (TRIUMPH-4, TRIUMPH-1) with osteoarthritis-pain and dysesthesia rows. Grade held at B pending peer-reviewed publication."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"tirzepatide","name":"Tirzepatide","aliases":["Mounjaro","Zepbound","dual GIP/GLP-1 agonist"],"url":"https://lyoresearch.com/compounds/tirzepatide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Tirzepatide is a once-weekly peptide that activates both GIP and GLP-1 receptors. It is approved for type 2 diabetes, weight management and obstructive sleep apnoea, and since August 2026 in the US to lower the risk of major cardiovascular events in adults with type 2 diabetes at high risk. In the only direct head-to-head trial it produced more weight loss than semaglutide (20.2% vs 13.7% at 72 weeks) with a similar side-effect profile. It is a prescription medicine; versions sold outside that channel are unlicensed.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"15+ RCTs","regulatory_status":"Approved (Rx)","molecule":{"formula":"C225H348N48O68","molecular_weight":"4813","cas":"2023788-19-2","pubchem_cid":166567236,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, once weekly","half_life":"About 5-6 days","licensed_regimen":"2.5 mg weekly for 4 weeks, then increase in 2.5 mg increments after at least 4 weeks on current dose; maintenance 5, 10 or 15 mg weekly (10 or 15 mg for OSA); maximum 15 mg weekly","product":"Zepbound","source":{"title":"Zepbound prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b"}},"outcomes":[{"outcome":"Body weight","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"10+ RCTs","evidence":"SURMOUNT-1: −20.9% at 72 weeks on 15 mg vs −3.1% placebo in 2,539 adults. SURMOUNT-5 head-to-head: −20.2% vs −13.7% on semaglutide at 72 weeks.","references":[{"citation":"Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1).","where":"N Engl J Med, 2022;387:205–216","url":"https://pubmed.ncbi.nlm.nih.gov/35658024/"},{"citation":"Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5).","where":"N Engl J Med, 2025;393(1):26–36","url":"https://pubmed.ncbi.nlm.nih.gov/40353578/"}],"verbatim":{"text":"The mean percentage change in weight at week 72 was -15.0% (95% confidence interval [CI], -15.9 to -14.2) with 5-mg weekly doses of tirzepatide, -19.5% (95% CI, -20.4 to -18.5) with 10-mg doses, and -20.9% (95% CI, -21.8 to -19.9) with 15-mg doses and -3.1% (95% CI, -4.3 to -1.9) with placebo (P<0.001 for all comparisons with placebo).","citation":"Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1).","url":"https://pubmed.ncbi.nlm.nih.gov/35658024/"}},{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"5 SURPASS RCTs","evidence":"SURPASS-2: HbA1c reductions of 2.0–2.3 points vs 1.9 on semaglutide 1 mg in type 2 diabetes.","references":[{"citation":"Frías JP, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2).","where":"N Engl J Med, 2021;385:503–515","url":"https://pubmed.ncbi.nlm.nih.gov/34170647/"}],"verbatim":{"text":"The estimated mean change from baseline in the glycated hemoglobin level was -2.01 percentage points, -2.24 percentage points, and -2.30 percentage points with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and -1.86 percentage points with semaglutide; the estimated differences between the 5-mg, 10-mg, and 15-mg tirzepatide groups and the semaglutide group were -0.15 percentage points (95% confidence interval [CI], -0.28 to -0.03; P = 0.02), -0.39 percentage points (95% CI, -0.51 to -0.26; P<0.001), and -0.45 percentage points (95% CI, -0.57 to -0.32; P<0.001), respectively.","citation":"Frías JP, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2).","url":"https://pubmed.ncbi.nlm.nih.gov/34170647/"}},{"outcome":"Obstructive sleep apnoea","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"2 RCTs","evidence":"SURMOUNT-OSA: apnoea–hypopnoea index fell by roughly 25–30 events per hour vs 5–6 on placebo; basis of the 2024 approval.","references":[{"citation":"Malhotra A, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA).","where":"N Engl J Med, 2024;391:1193–1205","url":"https://pubmed.ncbi.nlm.nih.gov/38912654/"}]},{"outcome":"Cardiovascular events","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"1 large outcomes RCT (n=13,165)","evidence":"SURPASS-CVOT, now published: tirzepatide was non-inferior to dulaglutide on major adverse cardiovascular events in type 2 diabetes. Superiority over an active GLP-1 comparator was not shown, and there is no placebo-controlled cardiovascular outcome trial. On this trial the FDA approved a cardiovascular risk-reduction indication on 28 August 2026; the grade and effect size do not change with the label.","references":[{"citation":"Nicholls SJ, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes (SURPASS-CVOT).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/41406444/"},{"citation":"Eli Lilly. FDA approves Lilly's Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes.","where":"Press release, 28 Aug 2026","url":"https://www.prnewswire.com/news-releases/fda-approves-lillys-mounjaro-tirzepatide-to-reduce-cardiovascular-risk-in-adults-with-type-2-diabetes-302862415.html"}],"verbatim":{"text":"A primary end-point event occurred in 801 patients (12.2%) in the tirzepatide group and 862 (13.1%) in the dulaglutide group (hazard ratio, 0.92; 95.3% confidence interval, 0.83 to 1.01; P = 0.003 for noninferiority; P = 0.09 for superiority).","citation":"Nicholls SJ, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes (SURPASS-CVOT).","url":"https://pubmed.ncbi.nlm.nih.gov/41406444/"}},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"All trials","evidence":"Nausea, diarrhoea and vomiting, mostly during dose escalation. In SURMOUNT-5, GI-related discontinuation was 2.7% vs 5.6% on semaglutide.","references":[{"citation":"Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1).","where":"N Engl J Med, 2022;387:205–216","url":"https://pubmed.ncbi.nlm.nih.gov/35658024/"},{"citation":"Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5).","where":"N Engl J Med, 2025;393(1):26–36","url":"https://pubmed.ncbi.nlm.nih.gov/40353578/"}],"verbatim":{"text":"The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation.","citation":"Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1).","url":"https://pubmed.ncbi.nlm.nih.gov/35658024/"}}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Mounjaro authorised via the EMA (2022; weight management added 2023). Grey-market versions are unlicensed medicines."},{"region":"United States","status":"Approved, prescription-only","note":"Mounjaro and Zepbound. On 28 August 2026 the FDA added an indication for Mounjaro to lower the risk of major adverse cardiovascular events in adults with type 2 diabetes at high risk, on the SURPASS-CVOT trial. The shortage was declared resolved in December 2024; compounding enforcement discretion has ended. More than 730 adverse-event reports for compounded versions by May 2026."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Mounjaro licensed by the MHRA. Counterfeit Zepbound/Mounjaro pens were among the products seized from illicit UK manufacturing sites in 2025–2026."},{"region":"Australia","status":"Registered, Schedule 4","note":"Mounjaro on the ARTG, prescription-only. Compounded tirzepatide has been unlawful since 1 October 2024."},{"region":"Canada","status":"Authorised, prescription-only","note":"Mounjaro and Zepbound carry a DIN. Vials sold online as tirzepatide were among the products Health Canada seized in August 2025."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the 2026 Prohibited List, and WADA confirmed on 21 September 2026 that GLP-1 receptor agonists stay off the 2027 List. Tirzepatide remains on WADA's Monitoring Program."}],"faq":[{"q":"Is tirzepatide better than semaglutide for weight loss?","a":"On the only head-to-head trial, yes: 20.2% versus 13.7% average loss at 72 weeks in 751 adults, with fewer people stopping for gut side effects on tirzepatide. Individual response varies a great deal."},{"q":"Is tirzepatide a peptide?","a":"Yes — a 39-amino-acid synthetic peptide based on the GIP hormone, modified to also activate GLP-1 receptors and to last about five days."},{"q":"What are the main side effects?","a":"Nausea, diarrhoea, vomiting and constipation, mostly while the dose is being increased. Rarer but serious: pancreatitis and gallbladder problems. It carries the same thyroid C-cell tumour warning as other GLP-1 drugs, based on rodent findings."},{"q":"Does the weight come back after stopping?","a":"Largely. In SURMOUNT-4, people switched to placebo after 36 weeks regained about half of what they had lost within a year, while those who continued kept losing."}],"references":[{"cite":"Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1).","where":"N Engl J Med, 2022;387:205–216","url":"https://pubmed.ncbi.nlm.nih.gov/35658024/","note":"2,539 adults; −20.9% at 72 weeks on 15 mg."},{"cite":"Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5).","where":"N Engl J Med, 2025;393(1):26–36","url":"https://pubmed.ncbi.nlm.nih.gov/40353578/","note":"751 adults, 72 weeks; −20.2% vs −13.7%; waist −18.4 cm vs −13.0 cm."},{"cite":"Frías JP, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes (SURPASS-2).","where":"N Engl J Med, 2021;385:503–515","url":"https://pubmed.ncbi.nlm.nih.gov/34170647/","note":"1,879 adults; HbA1c and weight vs semaglutide 1 mg."},{"cite":"Malhotra A, et al. Tirzepatide for the treatment of obstructive sleep apnea and obesity (SURMOUNT-OSA).","where":"N Engl J Med, 2024;391:1193–1205","url":"https://pubmed.ncbi.nlm.nih.gov/38912654/","note":"Two trials, 469 adults; basis of the sleep-apnoea approval."},{"cite":"Nicholls SJ, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes (SURPASS-CVOT).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/41406444/","note":"13,165 analysed; non-inferior to dulaglutide, superiority not shown."},{"cite":"Eli Lilly. FDA approves Lilly's Mounjaro (tirzepatide) to reduce cardiovascular risk in adults with type 2 diabetes.","where":"Press release, 28 Aug 2026","url":"https://www.prnewswire.com/news-releases/fda-approves-lillys-mounjaro-tirzepatide-to-reduce-cardiovascular-risk-in-adults-with-type-2-diabetes-302862415.html","note":"Indication based on SURPASS-CVOT (13,299 randomised; hazard ratio 0.92, 95.3% CI 0.83–1.01 vs dulaglutide)."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"WADA's 2027 List status (published 21 Sep 2026) added to the sport row. No change to the evidence or grades."},{"date":"2026-09-23","note":"US cardiovascular risk-reduction indication (28 Aug 2026) added to the answer and the US status row. Grades unchanged: the approval rests on the non-inferiority trial already cited."},{"date":"2026-09-02","note":"Full page. Added HbA1c, sleep-apnoea and cardiovascular rows; SURMOUNT-5 head-to-head figures; FAQ and regional status."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"tesamorelin","name":"Tesamorelin","aliases":["Egrifta","GHRH analogue","TH9507"],"url":"https://lyoresearch.com/compounds/tesamorelin","class":{"id":"ghrh-analogues","name":"GHRH analogues","url":"https://lyoresearch.com/classes/ghrh-analogues"},"summary":"Tesamorelin is a synthetic analogue of growth-hormone-releasing hormone, approved in the United States to reduce excess abdominal fat in people with HIV-associated lipodystrophy. In that population it cuts visceral fat by about 15% over six months, and the fat returns when treatment stops. Its use for general fat loss, muscle or anti-ageing rests on extrapolation from that specific group; there are no trials in healthy adults. It is not authorised in the EU.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"Several RCTs","regulatory_status":"Approved (Rx, US)","molecule":{"formula":"C221H366N72O67S","molecular_weight":"5136","cas":"218949-48-5","pubchem_cid":16137828,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, once daily","half_life":"About 8 minutes","licensed_regimen":"1.4 mg (0.35 mL reconstituted) subcutaneously once daily","product":"Egrifta SV","source":{"title":"Egrifta SV prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3d783378-b02d-4f19-99dd-0fc91a042224"}},"outcomes":[{"outcome":"Visceral fat (HIV lipodystrophy)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"2 phase 3 RCTs (n=816)","evidence":"Pooled phase 3: visceral adipose tissue −15.2% at 26 weeks vs +5% on placebo; effect lost within 26 weeks of stopping.","references":[{"citation":"Falutz J, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: pooled analysis of two phase 3 trials.","where":"J Acquir Immune Defic Syndr, 2010;53:311–322","url":"https://pubmed.ncbi.nlm.nih.gov/20554713/"}],"verbatim":{"text":"At wk 26, VAT decreased significantly in tesamorelin-treated patients (-24 ± 41 vs. 2 ± 35 cm(2), tesamorelin vs. placebo, P < 0.001; treatment effect, -15.4%).","citation":"Falutz J, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: pooled analysis of two phase 3 trials.","url":"https://pubmed.ncbi.nlm.nih.gov/20554713/"}},{"outcome":"Liver fat (HIV with NAFLD)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 RCT (n=61)","evidence":"Hepatic fat fraction fell by about a third over 12 months vs placebo; a specific population, one trial.","references":[{"citation":"Stanley TL, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, placebo-controlled trial.","where":"Lancet HIV, 2019","url":"https://pubmed.ncbi.nlm.nih.gov/31611038/"}],"verbatim":{"text":"Patients receiving tesamorelin had a greater reduction of HFF than did patients receiving placebo, with an absolute effect size of -4·1% (95% CI -7·6 to -0·7, p=0·018), corresponding to a -37% (95% CI -67 to -7, p=0·016) relative reduction from baseline.","citation":"Stanley TL, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, placebo-controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/31611038/"}},{"outcome":"Cognition in older adults","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 RCT (n=152)","evidence":"20 weeks of tesamorelin improved some executive-function measures in healthy older adults and those with mild cognitive impairment. Single trial, never replicated or developed further.","references":[{"citation":"Baker LD, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults.","where":"Arch Neurol, 2012;69:1420–1429","url":"https://pubmed.ncbi.nlm.nih.gov/22869065/"}],"verbatim":{"text":"The intent-to-treat analysis indicated a favorable effect of GHRH on cognition (P=.03), which was comparable in adults with MCI and healthy older adults.","citation":"Baker LD, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults.","url":"https://pubmed.ncbi.nlm.nih.gov/22869065/"}},{"outcome":"Fat loss in healthy adults","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Not studied. The approved population is not a proxy for the general public.","references":[]},{"outcome":"IGF-1 elevation and glucose effects","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":true,"human_studies":"Phase 3 programme","evidence":"Raises IGF-1 as intended; small rises in blood glucose and injection-site reactions are documented. Long-term cancer risk at elevated IGF-1 is the reason for the narrow label.","references":[{"citation":"Falutz J, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: pooled analysis of two phase 3 trials.","where":"J Acquir Immune Defic Syndr, 2010;53:311–322","url":"https://pubmed.ncbi.nlm.nih.gov/20554713/"}],"verbatim":{"text":"Mean IGF-I increased 108 ± 112 vs. -7 ± 64 ng/ml (P < 0.001 vs. placebo).","citation":"Falutz J, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: pooled analysis of two phase 3 trials.","url":"https://pubmed.ncbi.nlm.nih.gov/20554713/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"The Egrifta marketing authorisation application was withdrawn on 26 June 2012 after the CHMP could not conclude a positive benefit–risk balance."},{"region":"United States","status":"Approved (Egrifta), prescription-only","note":"Approved for excess abdominal fat in HIV-associated lipodystrophy. Prescribing outside that indication is a clinical decision; selling vials for 'research' is not a lawful supply route."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence. Unlicensed medicine when supplied for human use."},{"region":"Australia","status":"Not registered","note":"Not on the ARTG; prescription-only if obtained at all."},{"region":"Canada","status":"Authorised (Egrifta), prescription-only","note":"Authorised in Canada for HIV-associated abdominal fat. Vials sold online were nonetheless among the products Health Canada seized in August 2025."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"GHRH analogue: S2.2.4, growth hormone releasing factors."}],"faq":[{"q":"Does tesamorelin burn belly fat?","a":"In people with HIV-associated lipodystrophy, yes — about 15% less visceral fat after six months in two phase 3 trials. In anyone else it has not been tested, and the fat returns when treatment stops."},{"q":"Is tesamorelin the same as growth hormone?","a":"No. It prompts the body to release its own growth hormone rather than supplying it. The downstream effects overlap, including higher IGF-1."},{"q":"Is tesamorelin legal?","a":"It is a prescription medicine in the United States for one indication. It is not authorised in the EU or UK, and it is banned in sport."}],"references":[{"cite":"Falutz J, et al. Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: pooled analysis of two phase 3 trials.","where":"J Acquir Immune Defic Syndr, 2010;53:311–322","url":"https://pubmed.ncbi.nlm.nih.gov/20554713/","note":"816 participants; the approval basis."},{"cite":"Stanley TL, et al. Effects of tesamorelin on non-alcoholic fatty liver disease in HIV: a randomised, double-blind, placebo-controlled trial.","where":"Lancet HIV, 2019","url":"https://pubmed.ncbi.nlm.nih.gov/31611038/","note":"61 participants, 12 months."},{"cite":"Baker LD, et al. Effects of growth hormone-releasing hormone on cognitive function in adults with mild cognitive impairment and healthy older adults.","where":"Arch Neurol, 2012;69:1420–1429","url":"https://pubmed.ncbi.nlm.nih.gov/22869065/","note":"152 adults, 20 weeks; not replicated."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Full page. Added liver-fat, cognition and IGF-1 rows; regional status; FAQ."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"ipamorelin","name":"Ipamorelin","aliases":["GH secretagogue","ghrelin mimetic","NNC 26-0161"],"url":"https://lyoresearch.com/compounds/ipamorelin","class":{"id":"gh-secretagogues","name":"GH secretagogues (GHRPs)","url":"https://lyoresearch.com/classes/gh-secretagogues"},"summary":"Ipamorelin is a synthetic five-amino-acid peptide that stimulates growth-hormone release with little effect on cortisol or prolactin. Small early studies confirmed the hormone release; the only randomised trial — 117 bowel-surgery patients, testing it for post-operative gut recovery — found no benefit, and development stopped. It is not an approved medicine anywhere, and the popular claims about muscle, fat loss and sleep have never been tested in a trial.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"1 RCT (negative) + small early-phase","regulatory_status":"Not approved","molecule":{"formula":"C38H49N9O5","molecular_weight":"711.9","cas":"170851-70-4","pubchem_cid":9831659,"note":null},"pharmacokinetics":{"basis":"human","route":"Intravenous infusion in the human study; injected subcutaneously as sold","half_life":"About 2 hours (terminal, intravenous, healthy men)","licensed_regimen":null,"product":null,"source":{"title":"Gobburu JV, et al. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers. Pharm Res 1999;16:1412–1416","url":"https://pubmed.ncbi.nlm.nih.gov/10496658/"}},"outcomes":[{"outcome":"Growth hormone release","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"Small early-phase studies","evidence":"Acute, dose-dependent GH rises demonstrated in healthy volunteers in Novo Nordisk's early programme; more selective than GHRP-6, with little cortisol or prolactin rise.","references":[{"citation":"Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue.","where":"Eur J Endocrinol, 1998;139:552–561","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Raun+ipamorelin+selective+growth+hormone+secretagogue+1998"},{"citation":"Gobburu JV, et al. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers.","where":"Pharm Res, 1999;16:1412–1416","url":"https://pubmed.ncbi.nlm.nih.gov/10496658/"}]},{"outcome":"Post-operative ileus (gut recovery)","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 RCT (n=117)","evidence":"Median time to tolerate a solid meal 25.3 h vs 32.6 h on placebo — not statistically significant (p=0.15). No difference on secondary endpoints. Phase 3 was not pursued.","references":[{"citation":"Beck DE, Sweeney WB, McCarter MD, et al. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients.","where":"Int J Colorectal Dis, 2014;29:1527–1534","url":"https://link.springer.com/article/10.1007/s00384-014-2030-8"}],"verbatim":{"text":"Median time to first tolerated meal was 25.3 and 32.6 h in the ipamorelin and placebo groups, respectively (p = 0.15).","citation":"Beck DE, Sweeney WB, McCarter MD, et al. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients.","url":"https://link.springer.com/article/10.1007/s00384-014-2030-8"}},{"outcome":"Body composition","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None controlled","evidence":"No trial has measured muscle or fat change in people.","references":[]},{"outcome":"Sleep or recovery","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Unstudied in humans.","references":[]},{"outcome":"Safety in humans","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":true,"human_studies":"1 RCT + early-phase","evidence":"Well tolerated over seven days of IV dosing in the ileus trial. No long-term human safety data at the doses and durations used on the grey market.","references":[{"citation":"Beck DE, Sweeney WB, McCarter MD, et al. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients.","where":"Int J Colorectal Dis, 2014;29:1527–1534","url":"https://link.springer.com/article/10.1007/s00384-014-2030-8"}]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; 'research use only' labels do not change that."},{"region":"United States","status":"Not approved; compounding barred","note":"The advisory committee voted 0–12 against ipamorelin on 29 October 2024. Ipamorelin acetate remains in Category 2 for outsourcing facilities; its 503A nomination is listed as withdrawn (April 2026)."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it is an offence under the Human Medicines Regulations 2012; importing a small quantity purely for personal use is not itself an offence, but consignments are seized."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG. Obtainable only on prescription (compounded or imported under the Personal Importation Scheme with a prescription). Named in the TGA's April 2026 advisory. Named in NSW law as a prescribed restricted substance."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it is illegal. Among the products Health Canada seized from a domestic vendor in August 2025. Residents cannot import prescription drugs by mail."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Growth hormone secretagogue: S2.2.4."}],"faq":[{"q":"Does ipamorelin build muscle?","a":"Nobody knows. It releases growth hormone in the short term, but no trial has measured muscle or fat change in people taking it. The claim is an inference from the hormone, not a result."},{"q":"Is ipamorelin safe?","a":"It was well tolerated for a week of intravenous dosing in one trial of surgical patients. There is no human data on months of injections, which is how it is used outside medicine."},{"q":"Why was ipamorelin never approved?","a":"Its one proper randomised trial, for post-operative gut recovery, did not meet its endpoint, and the developer stopped. No company has tested it for any other indication."}],"references":[{"cite":"Raun K, et al. Ipamorelin, the first selective growth hormone secretagogue.","where":"Eur J Endocrinol, 1998;139:552–561","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Raun+ipamorelin+selective+growth+hormone+secretagogue+1998","note":"Pharmacology; animal and early human data."},{"cite":"Gobburu JV, et al. Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers.","where":"Pharm Res, 1999;16:1412–1416","url":"https://pubmed.ncbi.nlm.nih.gov/10496658/","note":"Dose–response for GH release in healthy adults."},{"cite":"Beck DE, Sweeney WB, McCarter MD, et al. Prospective, randomized, controlled, proof-of-concept study of the ghrelin mimetic ipamorelin for the management of postoperative ileus in bowel resection patients.","where":"Int J Colorectal Dis, 2014;29:1527–1534","url":"https://link.springer.com/article/10.1007/s00384-014-2030-8","note":"117 patients; primary endpoint not met (p=0.15)."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Full page. Added the negative post-operative-ileus RCT, safety row, regional status and FAQ."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"ghk-cu","name":"GHK-Cu","aliases":["copper peptide","copper tripeptide-1","glycyl-L-histidyl-L-lysine"],"url":"https://lyoresearch.com/compounds/ghk-cu","class":{"id":"healing-peptides","name":"Tissue-repair peptides","url":"https://lyoresearch.com/classes/healing-peptides"},"summary":"GHK-Cu is a naturally occurring three-amino-acid peptide that binds copper, found in plasma, saliva and urine, with levels that fall with age. Applied to skin in creams it has modest evidence from small trials for improving fine lines and skin firmness, which is why it is a common cosmetic ingredient. Injected use — increasingly promoted online — has no human evidence of any kind.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Small topical trials","regulatory_status":"Cosmetic ingredient","molecule":{"formula":"C14H21CuN6O4-","molecular_weight":"400.90","cas":null,"pubchem_cid":139035031,"note":"No CAS number listed on the PubChem record"},"pharmacokinetics":{"basis":"none","route":"Topical in the trials; injected as sold, with no human study","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Skin appearance (topical)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"3–4 small trials","evidence":"Twelve-week facial studies in the late 1990s and early 2000s reported improved skin laxity, clarity and fine lines versus vehicle or comparators. Small, short, largely industry-run.","references":[{"citation":"Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data.","where":"Int J Mol Sci, 2018;19:1987 (review)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Pickart+Margolina+GHK-Cu+2018+review"},{"citation":"Leyden JJ, et al. Skin care benefits of copper peptide containing facial cream.","where":"American Academy of Dermatology meeting, 2002 (abstract)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=copper+peptide+facial+cream+skin+laxity+12+week"}]},{"outcome":"Wound healing (topical)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Small trials, mixed","evidence":"A GHK-Cu gel was tested on diabetic foot ulcers in the 1990s with mixed results; the product was not carried forward.","references":[{"citation":"Mulder GD, et al. Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-L-histidyl-L-lysine copper.","where":"Wound Repair Regen, 1994;2:259–269","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Mulder+glycyl-histidyl-lysine+copper+diabetic+ulcers+1994"}]},{"outcome":"Hair growth","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None controlled","evidence":"Claims rest on cell and animal work and on analogy with minoxidil; no human trial.","references":[]},{"outcome":"Any outcome (injected)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Unstudied in humans. Injecting a copper complex without data on distribution or dose is not a safety-neutral act.","references":[]}],"regions":[{"region":"European Union","status":"Cosmetic ingredient; no medicinal authorisation","note":"Permitted in cosmetics. Injectable products presented for human use are unauthorised medicinal products."},{"region":"United States","status":"Cosmetic; injectable not approved","note":"Placed in Category 1 for non-injectable routes in 2023 (may be compounded topically pending review). The injectable nomination is listed as withdrawn since April 2026."},{"region":"United Kingdom","status":"Cosmetic; injectable unlicensed","note":"Lawful in topical cosmetics. Injectable products are unlicensed medicines."},{"region":"Australia","status":"Cosmetic; injectable unapproved","note":"Topical cosmetic use is unregulated as a medicine. Injectable GHK-Cu was named in the TGA's April 2026 advisory."},{"region":"Canada","status":"Cosmetic; injectable not authorised","note":"Injectable products have no DIN and cannot lawfully be sold."},{"region":"Sport (WADA)","status":"Not named","note":"Not listed. As a cosmetic it raises no doping question; injected as an unapproved drug it would fall under S0."}],"faq":[{"q":"Does GHK-Cu work for wrinkles?","a":"Modestly, in small twelve-week studies of topical products — improvements in fine lines, firmness and skin clarity versus vehicle. The trials are small and mostly industry-funded, so the honest answer is “probably a little.”"},{"q":"Is injecting GHK-Cu safe?","a":"Unknown. There are no human studies of injected GHK-Cu. Topical safety data does not transfer to injection."},{"q":"Does GHK-Cu regrow hair?","a":"No human trial has tested it. The claim comes from cell and animal studies and from its structural similarity to how minoxidil is thought to act."}],"references":[{"cite":"Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data.","where":"Int J Mol Sci, 2018;19:1987 (review)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Pickart+Margolina+GHK-Cu+2018+review","note":"Review by the peptide's discoverer; declared interest."},{"cite":"Leyden JJ, et al. Skin care benefits of copper peptide containing facial cream.","where":"American Academy of Dermatology meeting, 2002 (abstract)","url":"https://pubmed.ncbi.nlm.nih.gov/?term=copper+peptide+facial+cream+skin+laxity+12+week","note":"Twelve-week facial study; conference abstract, industry-supported."},{"cite":"Mulder GD, et al. Enhanced healing of ulcers in patients with diabetes by topical treatment with glycyl-L-histidyl-L-lysine copper.","where":"Wound Repair Regen, 1994;2:259–269","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Mulder+glycyl-histidyl-lysine+copper+diabetic+ulcers+1994","note":"Small trial of a GHK-Cu gel on diabetic foot ulcers."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Full page. Added wound-healing and hair rows, mechanism, regional status and FAQ."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"epitalon","name":"Epitalon","aliases":["Epithalon","Epithalone","AEDG peptide"],"url":"https://lyoresearch.com/compounds/epitalon","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"Epitalon is a synthetic four-amino-acid peptide (Ala-Glu-Asp-Gly) developed in St Petersburg in the 1980s and promoted for longevity on the basis of telomerase activation in cell culture and lifespan effects in mice. The human evidence comes from one research group, is uncontrolled, and much of it used Epithalamin — a pineal-gland extract — rather than the synthetic peptide sold under the name. It is not approved anywhere.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"Uncontrolled, single group","regulatory_status":"Not approved","molecule":{"formula":"C14H22N4O9","molecular_weight":"390.35","cas":"307297-39-8","pubchem_cid":219042,"note":null},"pharmacokinetics":{"basis":"none","route":"Injected or intranasal as sold; no human PK study","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Lifespan / mortality","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Uncontrolled, single group","evidence":"A 12–15-year observational follow-up of elderly patients from one institute reported lower mortality with Epithalamin (the extract) plus thymus extract. No randomisation, no blinding, and not the synthetic peptide.","references":[{"citation":"Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life.","where":"Neuro Endocrinol Lett, 2003;24:233–240","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Khavinson+Morozov+peptides+pineal+thymus+prolong+human+life+2003"}]},{"outcome":"Telomerase activation","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Cell culture only","evidence":"Telomerase activity and telomere lengthening reported in cultured human fibroblasts. Never measured in a living person.","references":[{"citation":"Khavinson VKh, et al. Peptide promotes overcoming of the division limit in human somatic cell.","where":"Bull Exp Biol Med, 2003;135:503–506","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Khavinson+epitalon+telomerase+human+somatic+cell+2003"}]},{"outcome":"Melatonin / sleep","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Small uncontrolled","evidence":"Small studies from the same group report restored night-time melatonin in elderly subjects; uncontrolled and unreplicated.","references":[{"citation":"Korkushko OV, et al. Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging.","where":"Bull Exp Biol Med, 2006;142:356–359","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Korkushko+epithalamine+elderly+accelerated+aging+2006"}]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None systematic","evidence":"No adverse-event data collected to modern standards. Unknown is not the same as safe.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; 'research use only' labels do not change that. Epithalamin products are authorised in Russia only."},{"region":"United States","status":"Not approved; compounding under review","note":"Removed from FDA's Category 2 list on 22 April 2026; the Pharmacy Compounding Advisory Committee recommended it for the 503A bulks list in July 2026 (recommended 24 July 2026). Not on the list yet and not an approved drug. Sold otherwise as an unapproved 'research chemical'."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it is an offence under the Human Medicines Regulations 2012; importing a small quantity purely for personal use is not itself an offence, but consignments are seized."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG. Possession without a prescription is an offence; imports without a prescription are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it is illegal. Residents cannot import prescription drugs by mail."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Not named, but unapproved anywhere, so it falls under S0 (non-approved substances)."}],"faq":[{"q":"Does epitalon extend lifespan?","a":"In mice, some studies from one group report modest lifespan effects. In humans there is no controlled evidence. The often-cited 12–15-year follow-up used Epithalamin, a pineal extract, not the synthetic peptide, and had no control group."},{"q":"Does epitalon lengthen telomeres?","a":"In cultured cells, one group has reported telomerase activation. It has never been measured in people taking the peptide."},{"q":"Is epitalon safe?","a":"Unknown. No systematic safety data exist. If it did activate telomerase in vivo, that would be a reason for caution, not reassurance."}],"references":[{"cite":"Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life.","where":"Neuro Endocrinol Lett, 2003;24:233–240","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Khavinson+Morozov+peptides+pineal+thymus+prolong+human+life+2003","note":"Uncontrolled long-term observation with Epithalamin (extract) and Thymalin."},{"cite":"Khavinson VKh, et al. Peptide promotes overcoming of the division limit in human somatic cell.","where":"Bull Exp Biol Med, 2003;135:503–506","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Khavinson+epitalon+telomerase+human+somatic+cell+2003","note":"Cell-culture telomerase and telomere findings."},{"cite":"Korkushko OV, et al. Geroprotective effect of epithalamine (pineal gland peptide preparation) in elderly subjects with accelerated aging.","where":"Bull Exp Biol Med, 2006;142:356–359","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Korkushko+epithalamine+elderly+accelerated+aging+2006","note":"Uncontrolled; Epithalamin extract, not the synthetic peptide."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Full page. Separated evidence for the synthetic peptide from evidence for the Epithalamin extract; added telomerase, melatonin and safety rows."},{"date":"2026-09-01","note":"Initial publication."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"tb-500","name":"TB-500","aliases":["thymosin beta-4 fragment","TB4","Tβ4"],"url":"https://lyoresearch.com/compounds/tb-500","class":{"id":"healing-peptides","name":"Tissue-repair peptides","url":"https://lyoresearch.com/classes/healing-peptides"},"summary":"TB-500 is a synthetic fragment of thymosin beta-4, a protein involved in cell migration and wound repair. Full-length thymosin beta-4 has been through phase 3 trials — as an eye drop for dry eye disease, with mixed results and no approval. The injected use people buy it for, for tendon and muscle injury, has never been tested in a completed human trial. It is banned in sport and not approved anywhere.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 for injected use","regulatory_status":"Not approved","molecule":{"formula":"C212H350N56O78S","molecular_weight":"4963","cas":"77591-33-4","pubchem_cid":16132341,"note":"PubChem record is full-length thymosin β4 (timbetasin); TB-500 as sold is a fragment of it"},"pharmacokinetics":{"basis":"human","route":"Intravenous in the only human study (full-length thymosin β4, healthy volunteers)","half_life":"Measured but not reported as a figure; the abstract says half-life increased with dose","licensed_regimen":null,"product":null,"source":{"title":"Ruff D, et al. A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. Ann N Y Acad Sci 2010","url":"https://pubmed.ncbi.nlm.nih.gov/20536472/"}},"outcomes":[{"outcome":"Tendon, muscle & ligament healing (injected)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 completed","evidence":"No completed phase 2 or 3 randomised trial has tested systemic thymosin beta-4 or TB-500 for tendinopathy, muscle strain or ligament injury. Animal models in rodents and rabbits only.","references":[{"citation":"Review of thymosin beta-4 / TB-500 clinical evidence: no completed systemic musculoskeletal RCT.","where":"Evidence review, 2026","url":"https://trimrx.com/blog/tb-500-research-review/"}]},{"outcome":"Dry eye disease (topical, RGN-259)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":false,"human_studies":"2 phase 3 RCTs","evidence":"ARISE-1 and ARISE-2 tested a pharmaceutical eye drop. Improvements on some ocular-surface measures; primary endpoints not consistently met, and no approval followed.","references":[{"citation":"RegeneRx. RGN-259 (thymosin beta-4 ophthalmic) ARISE-1 and ARISE-2 phase 3 trials in dry eye disease.","where":"Phase 3 programme; mixed endpoint results, no approval","url":"https://pubmed.ncbi.nlm.nih.gov/?term=RGN-259+thymosin+beta+4+dry+eye+ARISE"}]},{"outcome":"Cardiac repair","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Mouse and pig infarct models only.","references":[]},{"outcome":"Safety in humans (injected)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None systematic","evidence":"No systemic safety data. Independent testing of vendor products finds wide variation between labelled and actual content.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; 'research use only' labels do not change that."},{"region":"United States","status":"Not approved; compounding under review","note":"Removed from FDA's Category 2 list on 22 April 2026; the Pharmacy Compounding Advisory Committee recommended it for the 503A bulks list in July 2026 (8–6, 1 abstention). Not on the list yet and not an approved drug. Sold otherwise as an unapproved 'research chemical'."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it is an offence under the Human Medicines Regulations 2012; importing a small quantity purely for personal use is not itself an offence, but consignments are seized."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG. Obtainable only on prescription (compounded or imported under the Personal Importation Scheme with a prescription). Named in the TGA's April 2026 advisory. Named in NSW law as a prescribed restricted substance."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it is illegal. Among the products Health Canada seized from a domestic vendor in August 2025. Residents cannot import prescription drugs by mail."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"S2.3: 'thymosin-β4 and its derivatives, e.g. TB-500'."}],"faq":[{"q":"Does TB-500 heal injuries?","a":"Unknown in humans. The healing evidence is from rodent and rabbit models. No completed randomised trial has tested it for a human tendon, muscle or ligament injury."},{"q":"Is TB-500 the same as thymosin beta-4?","a":"No. TB-500 is a shorter synthetic fragment. The phase 3 trials used full-length pharmaceutical-grade thymosin beta-4, and they were eye drops."},{"q":"Is TB-500 banned in sport?","a":"Yes, since 1 January 2012, under WADA class S2 — prohibited at all times, in and out of competition."}],"references":[{"cite":"Review of thymosin beta-4 / TB-500 clinical evidence: no completed systemic musculoskeletal RCT.","where":"Evidence review, 2026","url":"https://trimrx.com/blog/tb-500-research-review/","note":"Secondary source; used for the absence-of-trials claim, which matches registry searches."},{"cite":"RegeneRx. RGN-259 (thymosin beta-4 ophthalmic) ARISE-1 and ARISE-2 phase 3 trials in dry eye disease.","where":"Phase 3 programme; mixed endpoint results, no approval","url":"https://pubmed.ncbi.nlm.nih.gov/?term=RGN-259+thymosin+beta+4+dry+eye+ARISE","note":"The only phase 3 human data for the parent molecule."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Initial publication. Injected use graded D; ophthalmic programme graded separately at B."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"cagrilintide","name":"Cagrilintide","aliases":["CagriSema (with semaglutide)","amylin analogue","AM833"],"url":"https://lyoresearch.com/compounds/cagrilintide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Cagrilintide is a once-weekly analogue of amylin, a hormone the pancreas releases alongside insulin that signals fullness. On its own it produced about 12% weight loss over 68 weeks; combined with semaglutide as CagriSema it produced 22.7% in a 3,417-person phase 3 trial published in the New England Journal of Medicine. Neither is approved yet, and the combination missed the 25% figure its developer had signalled.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"Phase 3 published","regulatory_status":"Investigational","molecule":{"formula":"C194H312N54O59S2","molecular_weight":"4409","cas":"1415456-99-3","pubchem_cid":171397054,"note":null},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, once weekly","half_life":"About 7–8 days (159–195 hours)","licensed_regimen":null,"product":null,"source":{"title":"Enebo LB, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg: a phase 1b trial. Lancet 2021","url":"https://www.sciencedirect.com/science/article/abs/pii/S014067362100845X"}},"outcomes":[{"outcome":"Body weight (with semaglutide, CagriSema)","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 large phase 3 RCT","evidence":"REDEFINE 1: −22.7% at 68 weeks in 3,417 adults vs −16.1% semaglutide alone, −11.8% cagrilintide alone, −2.3% placebo (trial-product estimand, i.e. while on treatment). The abstract's intention-to-treat figure is −20.4% vs −3.0%. 40.4% lost at least a quarter of body weight. The combination has its own page.","references":[{"citation":"Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","where":"N Engl J Med, 2025; DOI 10.1056/NEJMoa2502081","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2502081"}],"verbatim":{"text":"The estimated mean percent change in body weight from baseline to week 68 was -20.4% with cagrilintide-semaglutide as compared with -3.0% with placebo (estimated difference, -17.3 percentage points; 95% confidence interval, -18.1 to -16.6; P<0.001).","citation":"Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2502081"}},{"outcome":"Body weight (alone)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"Phase 2 + phase 3 arm","evidence":"−11.8% at 68 weeks as monotherapy in REDEFINE 1 — meaningful, but below the incretin drugs.","references":[{"citation":"Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","where":"N Engl J Med, 2025; DOI 10.1056/NEJMoa2502081","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2502081"}]},{"outcome":"GI side effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":true,"human_studies":"Phase 3","evidence":"Mostly mild-to-moderate nausea and vomiting, easing over time; the profile reported as consistent with GLP-1 drugs.","references":[{"citation":"Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","where":"N Engl J Med, 2025; DOI 10.1056/NEJMoa2502081","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2502081"}],"verbatim":{"text":"Gastrointestinal adverse events (affecting 79.6% in the cagrilintide-semaglutide group and 39.9% in the placebo group), including nausea, vomiting, diarrhea, constipation, or abdominal pain, were mainly transient and mild-to-moderate in severity.","citation":"Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2502081"}}],"regions":[{"region":"European Union","status":"Investigational; not authorised","note":"In phase 3 (with semaglutide as CagriSema). No authorisation; supply outside trials is unlawful."},{"region":"United States","status":"Investigational; cannot be compounded","note":"FDA: cagrilintide 'cannot be used in compounding under federal law'. Not a component of any approved drug."},{"region":"United Kingdom","status":"Unlicensed","note":"Investigational; supply outside trials is an offence."},{"region":"Australia","status":"Unapproved","note":"Not on the ARTG; prescription-only substance with no lawful supply outside trials."},{"region":"Canada","status":"Not authorised","note":"Investigational; no DIN."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so it falls under S0 (non-approved substances)."}],"faq":[{"q":"Is CagriSema better than semaglutide?","a":"In REDEFINE 1, yes: 22.7% versus 16.1% at 68 weeks in the same trial. It fell short of the 25% figure the market had expected, which is why the result was reported as a disappointment despite being the larger number."},{"q":"What is amylin?","a":"A hormone released with insulin after eating that signals fullness and slows stomach emptying. Cagrilintide is a version engineered to last about a week."},{"q":"Can you buy cagrilintide?","a":"Not legally. It is investigational; anything sold under the name is unlicensed and of unknown content."}],"references":[{"cite":"Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","where":"N Engl J Med, 2025; DOI 10.1056/NEJMoa2502081","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2502081","note":"3,417 adults, 68 weeks, four arms."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Initial publication from the published REDEFINE 1 trial."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"semax","name":"Semax","aliases":["ACTH(4-7)-Pro-Gly-Pro","heptapeptide nootropic"],"url":"https://lyoresearch.com/compounds/semax","class":{"id":"nootropic-peptides","name":"Nootropic and sleep peptides","url":"https://lyoresearch.com/classes/nootropic-peptides"},"summary":"Semax is a seven-amino-acid peptide derived from ACTH, developed in Russia in the 1980s and registered there for stroke and cognitive indications. It is not approved in the EU, US or UK. The human literature is almost entirely Russian-language, largely uncontrolled or poorly reported by international standards, and has not been replicated by independent groups — which is why the cognitive and stroke claims sit at grade D despite the registration.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"Russian-language, largely uncontrolled","regulatory_status":"Not approved (outside Russia)","molecule":{"formula":"C37H51N9O10S","molecular_weight":"813.9","cas":"80714-61-0","pubchem_cid":9811102,"note":null},"pharmacokinetics":{"basis":"animal","route":"Intranasal","half_life":"No human pharmacokinetic data; rat intranasal kinetics only","licensed_regimen":null,"product":null,"source":{"title":"Kinetics of Semax penetration into the brain and blood of rats after intranasal administration (Russian)","url":"https://pubmed.ncbi.nlm.nih.gov/16523722/"}},"outcomes":[{"outcome":"Cognitive performance","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Russian-language, mostly uncontrolled","evidence":"Small studies, often without blinding or a comparison group, published outside the indexed international literature. No independent replication.","references":[{"citation":"Searches of PubMed and trial registries for Semax human trials outside Russia.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Semax+randomized+controlled+trial"}]},{"outcome":"Stroke recovery","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Russian trials, not independently replicated","evidence":"The basis of the Russian registration. Not reproduced in trials meeting international reporting standards.","references":[{"citation":"Searches of PubMed and trial registries for Semax human trials outside Russia.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Semax+randomized+controlled+trial"}]},{"outcome":"Anxiety / stress","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None controlled internationally","evidence":"Claims derive from animal work and from the related peptide Selank.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"No systematic international data","evidence":"Long Russian clinical use is reassuring but not equivalent to pharmacovigilance data.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised in the EU","note":"Authorised in Russia only. Supplying it for human use in the EU is an offence under national medicines law."},{"region":"United States","status":"Not approved; compounding under review","note":"Removed from FDA's Category 2 list on 22 April 2026; the Pharmacy Compounding Advisory Committee recommended it for the 503A bulks list in July 2026 (recommended 24 July 2026). Not on the list yet and not an approved drug. Sold otherwise as an unapproved 'research chemical'."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence; supply for human use is an offence."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG. Possession without a prescription is an offence; imports without a prescription are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it is illegal. Residents cannot import prescription drugs by mail."},{"region":"Sport (WADA)","status":"Not on the list","note":"Approved in Russia, so S0 does not apply, and it is not named."}],"faq":[{"q":"Semax is approved in Russia — doesn't that count?","a":"It counts as a regulatory fact, not as evidence of effect at the standard LYO grades on. The trials behind the registration are largely unavailable in the indexed international literature and have not been independently replicated."},{"q":"Does Semax improve memory or focus?","a":"No trial meeting international standards has tested it. The claims come from small Russian studies and from animal work."}],"references":[{"cite":"Searches of PubMed and trial registries for Semax human trials outside Russia.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Semax+randomized+controlled+trial","note":"No randomised trials meeting international reporting standards were identified."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Initial publication. Graded D on absence of internationally reported controlled evidence; Russian registration noted separately."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"selank","name":"Selank","aliases":["tuftsin analogue","TP-7"],"url":"https://lyoresearch.com/compounds/selank","class":{"id":"nootropic-peptides","name":"Nootropic and sleep peptides","url":"https://lyoresearch.com/classes/nootropic-peptides"},"summary":"Selank is a synthetic analogue of tuftsin, an immune-signalling peptide, developed in Russia alongside Semax and registered there as an anxiolytic. Small Russian studies report anxiety reduction comparable to benzodiazepines without sedation; none has been replicated internationally or published to standards that allow the claim to be checked. It is not approved in the EU, US or UK.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"Russian-language, small","regulatory_status":"Not approved (outside Russia)","molecule":{"formula":"C33H57N11O9","molecular_weight":"751.9","cas":"129954-34-3","pubchem_cid":11765600,"note":null},"pharmacokinetics":{"basis":"none","route":"Intranasal as sold","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Anxiety","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Small Russian studies","evidence":"Reports of anxiety reduction in generalised anxiety disorder, some comparing against benzodiazepines. Small, from the originating institutes, not independently replicated.","references":[{"citation":"Searches of PubMed and trial registries for Selank human trials outside Russia.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Selank+anxiety+randomized+trial"}]},{"outcome":"Cognitive effects","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None controlled internationally","evidence":"Secondary claims from the same small studies.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"No systematic international data","evidence":"Reported as well tolerated in Russian use; no modern pharmacovigilance dataset.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised in the EU","note":"Authorised in Russia only. Supplying it for human use in the EU is an offence under national medicines law."},{"region":"United States","status":"Not approved","note":"Its 503A nomination is listed as withdrawn since April 2026 and it was not among the peptides reviewed in July 2026. Sold as an unapproved 'research chemical'."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence; supply for human use is an offence."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG. Possession without a prescription is an offence; imports without a prescription are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it is illegal. Residents cannot import prescription drugs by mail."},{"region":"Sport (WADA)","status":"Not on the list","note":"Approved in Russia, so S0 does not apply, and it is not named."}],"faq":[{"q":"Is Selank as effective as benzodiazepines?","a":"Some small Russian studies make that comparison. None has been replicated internationally, and the reporting does not allow the claim to be checked. Treat it as untested rather than established."},{"q":"Is Selank addictive?","a":"It is claimed not to be, on the basis that it does not act directly on benzodiazepine receptors. No long-term human study has examined dependence."}],"references":[{"cite":"Searches of PubMed and trial registries for Selank human trials outside Russia.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Selank+anxiety+randomized+trial","note":"No independently replicated randomised trials identified."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Initial publication. Graded D on absence of internationally reported controlled evidence."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"pt-141","name":"PT-141","aliases":["bremelanotide","Vyleesi","melanocortin agonist"],"url":"https://lyoresearch.com/compounds/pt-141","class":{"id":"melanocortins","name":"Melanocortin agonists","url":"https://lyoresearch.com/classes/melanocortins"},"summary":"PT-141, sold as Vyleesi, is a melanocortin-receptor agonist approved in the United States in 2019 for premenopausal women with hypoactive sexual desire disorder. Two phase 3 trials in 1,267 women found statistically significant but small improvements in desire and distress scores against placebo. Nausea affected 40% of participants and 18% stopped because of side effects. Use in men, and for erectile function, is unapproved and far less studied.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"2 phase 3 RCTs (n=1,267)","regulatory_status":"Approved (Rx, US)","molecule":{"formula":"C50H68N14O10","molecular_weight":"1025.2","cas":"189691-06-3","pubchem_cid":9941379,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, as needed before sexual activity","half_life":"About 2.7 hours","licensed_regimen":"1.75 mg subcutaneously at least 45 minutes before anticipated sexual activity; no more than 1 dose per 24 hours and no more than 8 doses per month","product":"Vyleesi (bremelanotide)","source":{"title":"Vyleesi prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f1d0c1b5-2f39-4bad-a6a4-0066e3ad5dcf"}},"outcomes":[{"outcome":"Sexual desire (premenopausal women, HSDD)","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"2 phase 3 RCTs","evidence":"RECONNECT studies, 24 weeks: FSFI desire-domain change +0.5 to +0.6 vs +0.2 on placebo. Statistically significant, clinically modest.","references":[{"citation":"VYLEESI (bremelanotide injection) US prescribing information — RECONNECT phase 3 studies (NCT02333071, NCT02338960).","where":"FDA label, initial US approval 2019","url":"https://www.accessdata.fda.gov/spl/data/3dca0cf9-a278-4c25-af93-d65f1f523504/3dca0cf9-a278-4c25-af93-d65f1f523504.xml"}],"verbatim":{"text":"From baseline to end-of-study, women taking bremelanotide had statistically significant increases in sexual desire (study 301: 0.30, P<.001; study 302: 0.42, P<.001; integrated studies 0.35, P<.001) and statistically significant reductions in distress related to low sexual desire (study 301: -0.37, P<.001; study 302: -0.29, P=.005; integrated studies -0.33, P<.001) compared with placebo.","citation":"Kingsberg SA, et al. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials (RECONNECT).","url":"https://pubmed.ncbi.nlm.nih.gov/31599840/"}},{"outcome":"Sexual distress (same population)","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"2 phase 3 RCTs","evidence":"Significant reduction in distress score versus placebo on the co-primary endpoint.","references":[{"citation":"VYLEESI (bremelanotide injection) US prescribing information — RECONNECT phase 3 studies (NCT02333071, NCT02338960).","where":"FDA label, initial US approval 2019","url":"https://www.accessdata.fda.gov/spl/data/3dca0cf9-a278-4c25-af93-d65f1f523504/3dca0cf9-a278-4c25-af93-d65f1f523504.xml"}]},{"outcome":"Erectile function / use in men","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Earlier phase 2 work","evidence":"Developed originally for erectile dysfunction; intranasal programme was stopped over blood-pressure increases. The approved product and indication are for women.","references":[{"citation":"VYLEESI (bremelanotide injection) US prescribing information — RECONNECT phase 3 studies (NCT02333071, NCT02338960).","where":"FDA label, initial US approval 2019","url":"https://www.accessdata.fda.gov/spl/data/3dca0cf9-a278-4c25-af93-d65f1f523504/3dca0cf9-a278-4c25-af93-d65f1f523504.xml"}]},{"outcome":"Nausea","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"Phase 3","evidence":"40% vs 1% on placebo; caused discontinuation in 8%. Overall discontinuation for adverse events 18% vs 2%.","references":[{"citation":"VYLEESI (bremelanotide injection) US prescribing information — RECONNECT phase 3 studies (NCT02333071, NCT02338960).","where":"FDA label, initial US approval 2019","url":"https://www.accessdata.fda.gov/spl/data/3dca0cf9-a278-4c25-af93-d65f1f523504/3dca0cf9-a278-4c25-af93-d65f1f523504.xml"}]},{"outcome":"Flushing and headache","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"Phase 3","evidence":"Flushing 20.3% vs 0.3%; headache 11.3% vs 1.9%; injection-site reactions 13.2% vs 8.4%.","references":[{"citation":"VYLEESI (bremelanotide injection) US prescribing information — RECONNECT phase 3 studies (NCT02333071, NCT02338960).","where":"FDA label, initial US approval 2019","url":"https://www.accessdata.fda.gov/spl/data/3dca0cf9-a278-4c25-af93-d65f1f523504/3dca0cf9-a278-4c25-af93-d65f1f523504.xml"}]}],"regions":[{"region":"European Union","status":"Not authorised","note":"Vyleesi has no EU marketing authorisation. Vials sold online are unauthorised medicinal products."},{"region":"United States","status":"Approved (Vyleesi), prescription-only","note":"Approved in 2019 for hypoactive sexual desire disorder in premenopausal women. 'Research' vials are unapproved drugs."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence; unlicensed medicine when supplied for human use."},{"region":"Australia","status":"Not registered","note":"Not on the ARTG; prescription-only substance."},{"region":"Canada","status":"Not authorised","note":"No DIN. Bremelanotide was among the products Health Canada seized in August 2025."},{"region":"Sport (WADA)","status":"Not on the list","note":"An approved drug that is not named in any section."}],"faq":[{"q":"Does PT-141 work?","a":"For its approved indication, yes, by a statistically significant but small margin: desire scores improved by about 0.5 points more than placebo on a scale where the clinical meaning of that difference is debated. It is approved because it beat placebo, not because the effect is large."},{"q":"Can men use PT-141?","a":"It is not approved for men. The original erectile-dysfunction programme was halted over blood-pressure increases with the intranasal formulation. Off-label use in men rests on far weaker evidence than the approval implies."},{"q":"Why does it cause so much nausea?","a":"Melanocortin receptors are involved in nausea pathways as well as arousal. Forty percent of trial participants experienced it, and 8% stopped because of it."}],"references":[{"cite":"VYLEESI (bremelanotide injection) US prescribing information — RECONNECT phase 3 studies (NCT02333071, NCT02338960).","where":"FDA label, initial US approval 2019","url":"https://www.accessdata.fda.gov/spl/data/3dca0cf9-a278-4c25-af93-d65f1f523504/3dca0cf9-a278-4c25-af93-d65f1f523504.xml","note":"1,267 premenopausal women across two 24-week trials; efficacy and adverse-event figures on this page come from the label."},{"cite":"Kingsberg SA, et al. Bremelanotide for the treatment of hypoactive sexual desire disorder: two randomized phase 3 trials (RECONNECT).","where":"Obstet Gynecol, 2019;134:899–908","url":"https://pubmed.ncbi.nlm.nih.gov/31599840/","note":"1,267 premenopausal women; peer-reviewed report of the two RECONNECT trials."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Initial publication from the FDA label and phase 3 programme."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"sermorelin","name":"Sermorelin","aliases":["GHRH(1-29)","Geref"],"url":"https://lyoresearch.com/compounds/sermorelin","class":{"id":"ghrh-analogues","name":"GHRH analogues","url":"https://lyoresearch.com/classes/ghrh-analogues"},"summary":"Sermorelin is the first 29 amino acids of growth-hormone-releasing hormone — the active fragment. It was FDA-approved in 1990 as Geref for diagnosing growth-hormone deficiency in children, and the brand was withdrawn in 2008 for commercial reasons, not safety. It reliably raises growth hormone and IGF-1. The adult anti-ageing and body-composition claims rest on small open-label studies, not randomised trials.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Approved paediatric use; small adult studies","regulatory_status":"Withdrawn (US brand)","molecule":{"formula":"C149H246N44O42S","molecular_weight":"3357.9","cas":"86168-78-7","pubchem_cid":16132413,"note":null},"pharmacokinetics":{"basis":"human","route":"Subcutaneous (former Geref product); intravenous and intranasal in the PK study","half_life":"Rapidly eliminated after intravenous injection (minutes); the figure is not in the accessible abstract. Intranasal bioavailability 3–5%","licensed_regimen":null,"product":null,"source":{"title":"Wilton P, et al. Pharmacokinetics of GHRH(1-29)-NH2 and stimulation of GH secretion in healthy subjects after intravenous or intranasal administration. Acta Paediatr Suppl 1993","url":"https://pubmed.ncbi.nlm.nih.gov/8329825/"}},"outcomes":[{"outcome":"Growth hormone / IGF-1 elevation","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Approval-grade paediatric data","evidence":"The basis of the 1990 approval as a diagnostic agent: a reliable, measurable GH response. Open-label adult series report IGF-1 rises over 3–6 months.","references":[{"citation":"Sermorelin evidence review: Geref approval history, withdrawal, and adult off-label data.","where":"Evidence review, 2026","url":"https://trimrx.com/blog/sermorelin-research-review/"}]},{"outcome":"Body composition in adults","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Small studies, mostly open-label","evidence":"A few small trials and open-label series report modest changes; no adequately powered randomised trial in healthy adults.","references":[{"citation":"Sermorelin evidence review: Geref approval history, withdrawal, and adult off-label data.","where":"Evidence review, 2026","url":"https://trimrx.com/blog/sermorelin-research-review/"}]},{"outcome":"Sleep quality","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Anecdotal / small","evidence":"Frequently claimed; the supporting human data is minimal and uncontrolled.","references":[]},{"outcome":"Safety in adults","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":true,"human_studies":"Compounding-era use","evidence":"Long clinical familiarity from the paediatric era and compounded adult use; no modern controlled long-term dataset.","references":[]}],"regions":[{"region":"European Union","status":"No current authorisation","note":"Historic Geref authorisations have lapsed; no product is authorised today. Supply for human use is an offence."},{"region":"United States","status":"Discontinued brand; compounded on prescription","note":"Geref was approved in 1997 and withdrawn from the market in 2008 for commercial reasons. Sermorelin acetate is not in Category 2 and is compounded by pharmacies on prescription; it remains unapproved as a product."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it is an offence under the Human Medicines Regulations 2012; importing a small quantity purely for personal use is not itself an offence, but consignments are seized."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG. Possession without a prescription is an offence; imports without a prescription are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it is illegal. Residents cannot import prescription drugs by mail."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"GHRH analogue: S2.2.4."}],"faq":[{"q":"Is sermorelin FDA-approved?","a":"It was, from 1990, as Geref — for diagnosing growth-hormone deficiency in children. The brand was withdrawn in 2008 for commercial reasons. It is not currently an approved product, though US compounding pharmacies supply it."},{"q":"Does sermorelin work for anti-ageing?","a":"It raises growth hormone and IGF-1, which is well established. Whether that produces the outcomes marketed under \"anti-ageing\" has not been shown in a randomised adult trial."},{"q":"Sermorelin or CJC-1295?","a":"Sermorelin has the regulatory history and a short half-life requiring daily dosing. CJC-1295 lasts far longer but never gained approval and has thinner human evidence. Neither has adult outcome trials."}],"references":[{"cite":"Sermorelin evidence review: Geref approval history, withdrawal, and adult off-label data.","where":"Evidence review, 2026","url":"https://trimrx.com/blog/sermorelin-research-review/","note":"Secondary source used for approval and withdrawal history; adult RCT data described as limited."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Initial publication. Hormone-elevation outcome graded A on approval-grade data; adult body-composition claims graded C."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"cjc-1295","name":"CJC-1295","aliases":["CJC-1295 DAC","modified GRF(1-29)","tesamorelin's cousin"],"url":"https://lyoresearch.com/compounds/cjc-1295","class":{"id":"ghrh-analogues","name":"GHRH analogues","url":"https://lyoresearch.com/classes/ghrh-analogues"},"summary":"CJC-1295 is a modified growth-hormone-releasing hormone fragment engineered to bind albumin so that it lasts days rather than minutes. Early human trials showed substantial, sustained rises in growth hormone and IGF-1 with weekly dosing. Development was discontinued and no trial has measured whether that translates into any clinical outcome. It is not approved anywhere and is banned in sport.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Early-phase only; programme discontinued","regulatory_status":"Not approved","molecule":{"formula":"C165H269N47O46","molecular_weight":"3647.2","cas":"446262-90-4","pubchem_cid":91971820,"note":"Record is CJC-1295 with DAC"},"pharmacokinetics":{"basis":"human","route":"Subcutaneous (healthy adults; the DAC form)","half_life":"About 6–8 days (CJC-1295 with DAC). No human data for the 'no-DAC' form","licensed_regimen":null,"product":null,"source":{"title":"Teichman SL, et al. Prolonged stimulation of growth hormone and IGF-I secretion by CJC-1295, a long-acting analog of GH-releasing hormone, in healthy adults. J Clin Endocrinol Metab 2006;91:799–805","url":"https://pubmed.ncbi.nlm.nih.gov/16352683/"}},"outcomes":[{"outcome":"Growth hormone / IGF-1 elevation","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"Phase 1 / early phase 2","evidence":"Weekly dosing produced sustained multi-fold GH increases and IGF-1 elevations over weeks in healthy adults — a large, reproducible effect on the marker.","references":[{"citation":"Teichman SL, et al. Prolonged stimulation of growth hormone and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GHRH, in healthy adults.","where":"J Clin Endocrinol Metab, 2006;91:799–805","url":"https://pubmed.ncbi.nlm.nih.gov/16352683/"}],"verbatim":{"text":"After a single injection of CJC-1295, there were dose-dependent increases in mean plasma GH concentrations by 2- to 10-fold for 6 d or more and in mean plasma IGF-I concentrations by 1.5- to 3-fold for 9-11 d.","citation":"Teichman SL, et al. Prolonged stimulation of growth hormone and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GHRH, in healthy adults.","url":"https://pubmed.ncbi.nlm.nih.gov/16352683/"}},{"outcome":"Body composition","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"No trial has measured muscle or fat change.","references":[]},{"outcome":"Any clinical outcome","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"The programme was discontinued before efficacy trials in any indication.","references":[]},{"outcome":"Safety in humans","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":true,"human_studies":"Early-phase only","evidence":"Short early-phase exposure only. Long-term safety of sustained IGF-1 elevation is unstudied.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; 'research use only' labels do not change that."},{"region":"United States","status":"Not approved; compounding barred","note":"The advisory committee excluded all five CJC-1295 forms on 4 December 2024; the nomination is listed as withdrawn since April 2026. Sold otherwise as an unapproved 'research chemical'."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it is an offence under the Human Medicines Regulations 2012; importing a small quantity purely for personal use is not itself an offence, but consignments are seized."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG. Obtainable only on prescription (compounded or imported under the Personal Importation Scheme with a prescription). Named in the TGA's April 2026 advisory. Named in NSW law as a prescribed restricted substance."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it is illegal. Among the products Health Canada seized from a domestic vendor in August 2025. Residents cannot import prescription drugs by mail."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"GHRH analogue: S2.2.4."}],"faq":[{"q":"Does CJC-1295 build muscle?","a":"Unknown. It raises growth hormone and IGF-1 substantially — that part is well documented in early trials. Whether that changes muscle or fat has never been measured in a trial."},{"q":"What is the difference between CJC-1295 with and without DAC?","a":"The DAC (drug affinity complex) version binds to albumin and lasts about a week. Without DAC it is essentially modified GRF(1-29), lasting around half an hour. They are sold under the same name."},{"q":"Why was development stopped?","a":"The programme was discontinued after early-phase work, without efficacy trials in any indication."}],"references":[{"cite":"Teichman SL, et al. Prolonged stimulation of growth hormone and insulin-like growth factor I secretion by CJC-1295, a long-acting analog of GHRH, in healthy adults.","where":"J Clin Endocrinol Metab, 2006;91:799–805","url":"https://pubmed.ncbi.nlm.nih.gov/16352683/","note":"The early-phase human pharmacology; no outcome endpoints."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Initial publication. Hormone effect graded B; all downstream outcomes D."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"aod-9604","name":"AOD-9604","aliases":["hGH fragment 176-191","lipolytic fragment"],"url":"https://lyoresearch.com/compounds/aod-9604","class":{"id":"growth-hormone-and-igf","name":"Growth hormone, IGF-1 and growth factors","url":"https://lyoresearch.com/classes/growth-hormone-and-igf"},"summary":"AOD-9604 is a fragment of human growth hormone developed specifically as an obesity drug. Unlike most peptides sold online, it was tested properly: pooled data across trials covering more than 900 participants found no statistically significant difference in fat mass or body weight against placebo. Development was terminated for lack of efficacy. It is still marketed for fat loss.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"900+ participants; no effect","regulatory_status":"Not approved","molecule":{"formula":"C78H123N23O23S2","molecular_weight":"1815.1","cas":"221231-10-3","pubchem_cid":71300630,"note":null},"pharmacokinetics":{"basis":"animal","route":"Oral and intravenous in the human trials, which report no PK","half_life":"No human pharmacokinetic data. Pig intravenous half-life about 3 minutes","licensed_regimen":null,"product":null,"source":{"title":"Stier H, Vos E, Kenley D. Safety and tolerability of the hexadecapeptide AOD9604 in humans. J Endocrinol Metab 2013;3:7–15","url":"https://www.jofem.org/index.php/jofem/article/view/157/194"}},"outcomes":[{"outcome":"Fat mass reduction","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Pooled trials, 900+ participants","evidence":"Early short studies suggested a signal; larger and longer trials did not replicate it. Pooled analysis found no significant difference versus placebo. Development terminated for lack of efficacy.","references":[{"citation":"Pooled analysis of published and unpublished AOD-9604 human trials (900+ participants): no significant difference in fat mass or body weight versus placebo.","where":"Evidence review, 2025","url":"https://www.pepcodex.com/blog/aod9604-human-efficacy"}]},{"outcome":"Body weight","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Pooled trials","evidence":"No significant difference from placebo.","references":[{"citation":"Pooled analysis of published and unpublished AOD-9604 human trials (900+ participants): no significant difference in fat mass or body weight versus placebo.","where":"Evidence review, 2025","url":"https://www.pepcodex.com/blog/aod9604-human-efficacy"}]},{"outcome":"Osteoarthritis / cartilage","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None conclusive","evidence":"A later development direction; no positive controlled human result.","references":[]},{"outcome":"Safety in humans","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":true,"human_studies":"Trial programme","evidence":"Generally well tolerated in the trials — which is the one thing a failed efficacy programme does establish.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; 'research use only' labels do not change that."},{"region":"United States","status":"Not approved; compounding barred","note":"The advisory committee voted 0–12 against AOD-9604 on 4 December 2024; the nomination is listed as withdrawn since April 2026."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it is an offence under the Human Medicines Regulations 2012; importing a small quantity purely for personal use is not itself an offence, but consignments are seized."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG. Possession without a prescription is an offence; imports without a prescription are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it is illegal. Among the products Health Canada seized from a domestic vendor in August 2025. Residents cannot import prescription drugs by mail."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"S2.2.3: growth hormone fragments, AOD-9604 named."}],"faq":[{"q":"Does AOD-9604 burn fat?","a":"Not in humans, on the available evidence. Pooled trial data across more than 900 participants found no significant difference from placebo in fat mass or body weight, and development was stopped for that reason."},{"q":"Why is it still sold if it failed?","a":"Failing an efficacy trial does not remove a compound from the grey market. It gained food-ingredient status in some jurisdictions, which is often quoted as though it were an approval."}],"references":[{"cite":"Pooled analysis of published and unpublished AOD-9604 human trials (900+ participants): no significant difference in fat mass or body weight versus placebo.","where":"Evidence review, 2025","url":"https://www.pepcodex.com/blog/aod9604-human-efficacy","note":"Secondary source summarising the trial programme and its termination for lack of efficacy."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Initial publication. Graded D on negative human trials — distinct from D for absence of trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"mots-c","name":"MOTS-c","aliases":["mitochondrial ORF of the twelve S rRNA type-c","mitochondrial-derived peptide"],"url":"https://lyoresearch.com/compounds/mots-c","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA rather than the nucleus, discovered in 2015. In mice it improves insulin sensitivity and protects against diet-induced obesity, and human blood levels fall with age and correlate with fitness. No controlled human trial has tested giving it to anyone. It is not approved anywhere.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 controlled","regulatory_status":"Not approved","molecule":{"formula":"C101H152N28O22S2","molecular_weight":"2174.6","cas":"1627580-64-6","pubchem_cid":146675088,"note":null},"pharmacokinetics":{"basis":"none","route":"Injected as sold; no human administration study","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Insulin sensitivity / metabolic health","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Mouse models of diet-induced obesity and insulin resistance. Human data is observational — levels correlate with fitness and fall with age — which cannot show what supplementation would do.","references":[]},{"outcome":"Exercise capacity","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Rodent exercise models; human correlation studies only.","references":[]},{"outcome":"Longevity","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Association studies of a mitochondrial variant in a Japanese cohort; not an intervention.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None","evidence":"No human dosing study of any kind.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; 'research use only' labels do not change that."},{"region":"United States","status":"Not approved; compounding under review","note":"Removed from FDA's Category 2 list on 22 April 2026; the Pharmacy Compounding Advisory Committee recommended it for the 503A bulks list in July 2026 (7–5, 2 abstentions). Not on the list yet and not an approved drug. Sold otherwise as an unapproved 'research chemical'."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it is an offence under the Human Medicines Regulations 2012; importing a small quantity purely for personal use is not itself an offence, but consignments are seized."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG. Possession without a prescription is an offence; imports without a prescription are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it is illegal. Residents cannot import prescription drugs by mail."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"S4.4.1 metabolic modulators: MOTS-c named. Sport Integrity Australia lists it among common prohibited peptides."}],"faq":[{"q":"Does MOTS-c improve metabolism in humans?","a":"Unknown. The metabolic effects are from mouse studies. Human research so far measures naturally occurring MOTS-c levels; it has never been given to people in a controlled trial."},{"q":"Why do people say it is linked to longevity?","a":"A mitochondrial variant affecting MOTS-c has been associated with longevity in a Japanese cohort. That is an association in people who inherited it, not a result of taking anything."}],"references":[{"cite":"Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.","where":"Cell Metab, 2015;21:443–454","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Lee+MOTS-c+mitochondrial+derived+peptide+2015+Cell+Metabolism","note":"The discovery paper; mouse models."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"date":"2026-09-02","note":"Initial publication. All outcomes graded D on absence of human intervention trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"liraglutide","name":"Liraglutide","aliases":["Saxenda","Victoza","GLP-1 receptor agonist","daily GLP-1"],"url":"https://lyoresearch.com/compounds/liraglutide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Liraglutide is a once-daily GLP-1 receptor agonist and the drug that proved the class. In the 3,731-person SCALE trial it produced 8.0% weight loss at 56 weeks against 2.6% on placebo, and in the 9,340-person LEADER trial it cut major cardiovascular events by 13% and cardiovascular death by 22% in people with type 2 diabetes. It is approved almost everywhere, now generic, and less effective than the weekly drugs that followed it.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"20+ RCTs","regulatory_status":"Approved (Saxenda, Victoza)","molecule":{"formula":"C172H265N43O51","molecular_weight":"3751","cas":"204656-20-2","pubchem_cid":16134956,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, once daily","half_life":"About 13 hours","licensed_regimen":"0.6 mg daily for 1 week, increase by 0.6 mg weekly (1.2, 1.8, 2.4 mg); maintenance 3 mg daily from week 5","product":"Saxenda","source":{"title":"Saxenda prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3946d389-0926-4f77-a708-0acb8153b143"}},"outcomes":[{"outcome":"Body weight (adults)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"5 SCALE RCTs","evidence":"SCALE Obesity and Prediabetes, 3,731 adults, 56 weeks: −8.0% on liraglutide 3.0 mg versus −2.6% on placebo; 63% versus 27% lost at least 5%, 33% versus 11% at least 10%.","references":[{"citation":"Pi-Sunyer X, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management (SCALE Obesity and Prediabetes).","where":"N Engl J Med, 2015; DOI 10.1056/NEJMoa1411892","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1411892"}],"verbatim":{"text":"At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P<0.001, with last-observation-carried-forward imputation).","citation":"Pi-Sunyer X, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management (SCALE Obesity and Prediabetes).","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1411892"}},{"outcome":"Major cardiovascular events","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"1 large outcome RCT","evidence":"LEADER, 9,340 people with type 2 diabetes, median 3.8 years: MACE 13.0% versus 14.9% (hazard ratio 0.87, 95% CI 0.79–0.97); cardiovascular death HR 0.78; all-cause death HR 0.85.","references":[{"citation":"Marso SP, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER).","where":"N Engl J Med, 2016; DOI 10.1056/NEJMoa1603827","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1603827"}],"verbatim":{"text":"The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority).","citation":"Marso SP, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER).","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1603827"}},{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"LEAD programme, 6 RCTs","evidence":"The original approval basis (Victoza, 2009–2010): HbA1c reductions of roughly 1–1.5 percentage points across the LEAD trials.","references":[{"citation":"Liraglutide (Victoza) prescribing information and the LEAD trial programme.","where":"FDA label","url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022341"}]},{"outcome":"Body weight (adolescents 12–17)","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"1 RCT","evidence":"SCALE Teens, 251 adolescents, 56 weeks: BMI standard-deviation score −0.23 versus −0.00; the first GLP-1 approval for under-18s.","references":[{"citation":"Kelly AS, et al. A randomized, controlled trial of liraglutide for adolescents with obesity (SCALE Teens).","where":"N Engl J Med, 2020; DOI 10.1056/NEJMoa1916038","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1916038"}],"verbatim":{"text":"Liraglutide was superior to placebo with regard to the change from baseline in the BMI standard-deviation score at week 56 (estimated difference, -0.22; 95% confidence interval [CI], -0.37 to -0.08; P = 0.002).","citation":"Kelly AS, et al. A randomized, controlled trial of liraglutide for adolescents with obesity (SCALE Teens).","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1916038"}},{"outcome":"Body weight (children 6–11)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 RCT","evidence":"SCALE Kids, 82 children, 56 weeks: BMI −5.8% versus +1.6% on placebo. One small trial; not yet a licensed indication in most jurisdictions.","references":[{"citation":"Fox CK, et al. Liraglutide for children 6 to <12 years of age with obesity (SCALE Kids).","where":"N Engl J Med, 2024; DOI 10.1056/NEJMoa2407379","url":"https://www.nejm.org/doi/10.1056/NEJMoa2407379"}],"verbatim":{"text":"At week 56, the mean percentage change from baseline in BMI was -5.8% with liraglutide and 1.6% with placebo, representing an estimated difference of -7.4 percentage points (95% confidence interval [CI], -11.6 to -3.2; P<0.001).","citation":"Fox CK, et al. Liraglutide for children 6 to <12 years of age with obesity (SCALE Kids).","url":"https://www.nejm.org/doi/10.1056/NEJMoa2407379"}},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"All trials","evidence":"Nausea in roughly 40% at the 3.0 mg dose in SCALE, vomiting and diarrhoea common; about 10% stopped for adverse events versus 4% on placebo.","references":[{"citation":"Pi-Sunyer X, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management (SCALE Obesity and Prediabetes).","where":"N Engl J Med, 2015; DOI 10.1056/NEJMoa1411892","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1411892"}],"verbatim":{"text":"The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea.","citation":"Pi-Sunyer X, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management (SCALE Obesity and Prediabetes).","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1411892"}},{"outcome":"Gallbladder events","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":true,"human_studies":"SCALE + LEADER","evidence":"Cholelithiasis and cholecystitis were more frequent on liraglutide (2.5% versus 1.0% in SCALE), a class effect partly explained by rapid weight loss.","references":[{"citation":"Pi-Sunyer X, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management (SCALE Obesity and Prediabetes).","where":"N Engl J Med, 2015; DOI 10.1056/NEJMoa1411892","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1411892"},{"citation":"Marso SP, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER).","where":"N Engl J Med, 2016; DOI 10.1056/NEJMoa1603827","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1603827"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Victoza (2009) and Saxenda (2015) authorised via the EMA; generics authorised from 2024."},{"region":"United States","status":"Approved, prescription-only","note":"Victoza (2010), Saxenda (2014); first generic liraglutide launched 2024. Compounded copies are not permitted now that approved generics exist."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Victoza and Saxenda licensed; Saxenda available on the NHS through specialist weight-management services."},{"region":"Australia","status":"Registered, Schedule 4","note":"Victoza and Saxenda on the ARTG. Compounded GLP-1 copies unlawful since 1 October 2024."},{"region":"Canada","status":"Authorised, prescription-only","note":"Victoza and Saxenda carry a DIN."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the 2026 Prohibited List."}],"faq":[{"q":"Is liraglutide as good as semaglutide for weight loss?","a":"No. In the head-to-head STEP 8 trial, semaglutide 2.4 mg weekly produced 15.8% weight loss at 68 weeks against 6.4% for liraglutide 3.0 mg daily. Liraglutide's advantages are price, availability and a longer safety record."},{"q":"Does liraglutide protect the heart?","a":"In people with type 2 diabetes at high cardiovascular risk, yes: LEADER showed a 13% relative reduction in major cardiovascular events and a 22% reduction in cardiovascular death over a median 3.8 years. That trial did not include people without diabetes."},{"q":"Is there a generic?","a":"Yes. Generic liraglutide for diabetes reached the US market in 2024 and for obesity in 2025, with EU generics from 2024. It is the only GLP-1 obesity drug currently off patent."},{"q":"Can children take it?","a":"It is approved for adolescents from 12 on the strength of SCALE Teens. For children aged 6–11 there is one 82-child trial (SCALE Kids, 2024) showing a 7-point BMI difference versus placebo; regulators are reviewing that age group."}],"references":[{"cite":"Pi-Sunyer X, et al. A randomized, controlled trial of 3.0 mg of liraglutide in weight management (SCALE Obesity and Prediabetes).","where":"N Engl J Med, 2015; DOI 10.1056/NEJMoa1411892","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1411892","note":"3,731 adults, 56 weeks."},{"cite":"Marso SP, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes (LEADER).","where":"N Engl J Med, 2016; DOI 10.1056/NEJMoa1603827","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1603827","note":"9,340 patients, median 3.8 years."},{"cite":"Liraglutide (Victoza) prescribing information and the LEAD trial programme.","where":"FDA label","url":"https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=022341","note":"HbA1c data from six phase 3 trials."},{"cite":"Kelly AS, et al. A randomized, controlled trial of liraglutide for adolescents with obesity (SCALE Teens).","where":"N Engl J Med, 2020; DOI 10.1056/NEJMoa1916038","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1916038","note":"251 adolescents, 56 weeks."},{"cite":"Fox CK, et al. Liraglutide for children 6 to <12 years of age with obesity (SCALE Kids).","where":"N Engl J Med, 2024; DOI 10.1056/NEJMoa2407379","url":"https://www.nejm.org/doi/10.1056/NEJMoa2407379","note":"82 children, 56 weeks."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication from the SCALE, LEADER and paediatric trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"survodutide","name":"Survodutide","aliases":["BI 456906","GLP-1/glucagon dual agonist","Boehringer Ingelheim / Zealand"],"url":"https://lyoresearch.com/compounds/survodutide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Survodutide is a once-weekly peptide that activates both the GLP-1 and glucagon receptors. In SYNCHRONIZE-1, a 725-person phase 3 trial published in June 2026, it produced 12–13% weight loss at 76 weeks against 5% on placebo, with gastrointestinal symptoms in up to 90% of participants. In people who also have type 2 diabetes the figure was 8–10% against 4% (SYNCHRONIZE-2, published October 2026). Its distinctive result is in the liver: a phase 2 trial resolved MASH without worsening fibrosis in 83% of patients at the top dose. It is not approved anywhere.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"2 phase 3 RCTs published (n=725; n=752)","regulatory_status":"Investigational","molecule":{"formula":"C192H289N47O61","molecular_weight":"4232","cas":"2805997-46-8","pubchem_cid":171378821,"note":null},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, once weekly","half_life":"About 6 days","licensed_regimen":null,"product":null,"source":{"title":"Lawitz EJ, et al. Efficacy, tolerability and pharmacokinetics of survodutide in cirrhosis. J Hepatol 2024;81","url":"https://www.sciencedirect.com/science/article/pii/S0168827824023031"}},"outcomes":[{"outcome":"Body weight","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT + phase 2","evidence":"SYNCHRONIZE-1, 725 adults, 76 weeks: −12% (3.6 mg) and −13% (6.0 mg) versus −5% placebo; at least 5% loss in 73%, 72% and 46%. Phase 2: up to −14.9% at 46 weeks.","references":[{"citation":"Survodutide in adults with obesity: SYNCHRONIZE-1, a randomised, double-blind, placebo-controlled phase 3 trial.","where":"N Engl J Med, published online 7 June 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+SYNCHRONIZE-1"},{"citation":"le Roux CW, et al. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.","where":"Lancet Diabetes Endocrinol, 2024","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+obesity+phase+2+le+Roux"}],"verbatim":{"text":"At week 76, the mean change in body weight from baseline according to the treatment-regimen estimand was -12.2% (95% confidence interval [CI], -13.6 to -10.8) in the 3.6-mg group, -13.0% (95% CI, -14.4 to -11.6) in the 6.0-mg group, and -5.4% (95% CI, -6.9 to -4.0) in the placebo group; 72.6%, 71.9% and 46.3% of the participants, respectively, had weight reduction of at least 5% (P<0.001 for all comparisons with placebo).","citation":"Survodutide in adults with obesity: SYNCHRONIZE-1, a randomised, double-blind, placebo-controlled phase 3 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+SYNCHRONIZE-1"}},{"outcome":"Body weight (obesity with type 2 diabetes)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT (n=752, 76 wk)","evidence":"SYNCHRONIZE-2, published in the New England Journal of Medicine on 1 October 2026: −8.2% (3.6 mg) and −9.8% (6.0 mg) versus −3.9% on placebo at 76 weeks, counting all participants whether or not they stayed on treatment; at least 5% loss in 57.6%, 64.5% and 35.1%. HbA1c fell 0.9 and 0.8 points against 0.2, from a baseline of 7.4%. The usual pattern: less weight loss when type 2 diabetes is present.","references":[{"citation":"Wharton S, et al. Survodutide once weekly in adults with obesity and type 2 diabetes (SYNCHRONIZE-2).","where":"N Engl J Med, 2026 (online 1 Oct)","url":"https://pubmed.ncbi.nlm.nih.gov/42820639/"}],"verbatim":{"text":"The mean weight change at week 76 according to the treatment-regimen estimand (which assessed effects regardless of whether the trial regimen was discontinued or interrupted or whether other antiobesity therapies were used) was -8.2% (95% confidence interval [CI], -9.2 to -7.2) in the 3.6-mg group, -9.8% (95% CI, -10.8 to -8.8) in the 6.0-mg group, and -3.9% (95% CI, -4.9 to -2.9) in the placebo group; weight reduction of at least 5% occurred in 57.6%, 64.5%, and 35.1% of the participants, respectively (P<0.001 for all comparisons with placebo).","citation":"Wharton S, et al. Survodutide once weekly in adults with obesity and type 2 diabetes (SYNCHRONIZE-2).","url":"https://pubmed.ncbi.nlm.nih.gov/42820639/"}},{"outcome":"Liver disease (MASH resolution)","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 phase 2 RCT; phase 3 running","evidence":"Phase 2 in 293 patients: MASH improvement without worsening fibrosis in 83% at 4.8 mg versus 18% on placebo at 48 weeks; fibrosis improvement in 52% versus 26%. Phase 3 LIVERAGE ongoing.","references":[{"citation":"Sanyal AJ, et al. A phase 2 randomized trial of survodutide in MASH and fibrosis.","where":"N Engl J Med, 2024; DOI 10.1056/NEJMoa2401755","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2401755"}]},{"outcome":"Liver fat and visceral fat","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"Phase 3 (SYNCHRONIZE-MASLD)","evidence":"Marked reductions in liver fat and visceral fat reported in the phase 3 obesity-with-MASLD trial; consistent with the glucagon component's hepatic action.","references":[{"citation":"Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a phase 3 trial.","where":"2026","url":"https://pubmed.ncbi.nlm.nih.gov/42252333/"}]},{"outcome":"GI side effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":true,"human_studies":"Phase 3","evidence":"Mild-to-moderate gastrointestinal symptoms in 81% (3.6 mg) and 90% (6.0 mg) versus 48% on placebo in SYNCHRONIZE-1, with substantial discontinuation. SYNCHRONIZE-2: 72.8% and 77.7% versus 38.6%, generally mild to moderate and transient.","references":[{"citation":"Survodutide in adults with obesity: SYNCHRONIZE-1, a randomised, double-blind, placebo-controlled phase 3 trial.","where":"N Engl J Med, published online 7 June 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+SYNCHRONIZE-1"},{"citation":"Wharton S, et al. Survodutide once weekly in adults with obesity and type 2 diabetes (SYNCHRONIZE-2).","where":"N Engl J Med, 2026 (online 1 Oct)","url":"https://pubmed.ncbi.nlm.nih.gov/42820639/"}]},{"outcome":"Heart rate increase","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"Phase 2 + 3","evidence":"Resting heart rate rises a few beats per minute, as with other glucagon-receptor agonists; long-term significance unknown.","references":[{"citation":"le Roux CW, et al. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.","where":"Lancet Diabetes Endocrinol, 2024","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+obesity+phase+2+le+Roux"}]}],"regions":[{"region":"European Union","status":"Investigational; not authorised","note":"Phase 3; no marketing authorisation. Supply outside trials is unlawful."},{"region":"United States","status":"Investigational; not approved","note":"Phase 3; FDA has warned sellers marketing 'research' survodutide for human use. Cannot be compounded."},{"region":"United Kingdom","status":"Unlicensed","note":"Investigational; supply outside trials is an offence."},{"region":"Australia","status":"Unapproved","note":"Not on the ARTG; no lawful supply outside trials."},{"region":"Canada","status":"Not authorised","note":"Investigational; no DIN."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so it falls under S0 (non-approved substances)."}],"faq":[{"q":"How much weight does survodutide cause people to lose?","a":"In the phase 3 SYNCHRONIZE-1 trial, 12–13% over 76 weeks against 5% on placebo — less than tirzepatide's roughly 20% in its own trials, though trials are not directly comparable."},{"q":"Why is survodutide talked about for liver disease?","a":"Because its glucagon component acts on the liver. In a phase 2 trial, 83% of patients on the top dose had MASH resolve without worsening fibrosis, against 18% on placebo — among the strongest liver results of any drug in the class."},{"q":"Is survodutide available?","a":"No. It is investigational everywhere. The FDA has specifically warned companies selling it as a research chemical for human use."}],"references":[{"cite":"Survodutide in adults with obesity: SYNCHRONIZE-1, a randomised, double-blind, placebo-controlled phase 3 trial.","where":"N Engl J Med, published online 7 June 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+SYNCHRONIZE-1","note":"725 adults, 76 weeks, 3.6 mg and 6.0 mg versus placebo."},{"cite":"le Roux CW, et al. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.","where":"Lancet Diabetes Endocrinol, 2024","url":"https://pubmed.ncbi.nlm.nih.gov/?term=survodutide+obesity+phase+2+le+Roux","note":"387 adults, 46 weeks."},{"cite":"Sanyal AJ, et al. A phase 2 randomized trial of survodutide in MASH and fibrosis.","where":"N Engl J Med, 2024; DOI 10.1056/NEJMoa2401755","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa2401755","note":"293 patients, 48 weeks."},{"cite":"Survodutide in adults with obesity and metabolic dysfunction-associated steatotic liver disease: SYNCHRONIZE-MASLD, a phase 3 trial.","where":"2026","url":"https://pubmed.ncbi.nlm.nih.gov/42252333/","note":"Liver-fat and visceral-fat outcomes."},{"cite":"Wharton S, et al. Survodutide once weekly in adults with obesity and type 2 diabetes (SYNCHRONIZE-2).","where":"N Engl J Med, 2026 (online 1 Oct)","url":"https://pubmed.ncbi.nlm.nih.gov/42820639/","note":"752 adults, 76 weeks, 3.6 mg and 6.0 mg versus placebo. NCT06066528."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"SYNCHRONIZE-2 (N Engl J Med, 1 Oct 2026) added as a new row for obesity with type 2 diabetes, graded B: −8.2% and −9.8% versus −3.9% at 76 weeks. Other grades unchanged."},{"date":"2026-09-03","note":"Initial publication from SYNCHRONIZE-1 and the phase 2 MASH trial."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"mazdutide","name":"Mazdutide","aliases":["IBI362","LY3305677","GLP-1/glucagon dual agonist","Innovent / Lilly"],"url":"https://lyoresearch.com/compounds/mazdutide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Mazdutide is a once-weekly GLP-1/glucagon dual agonist developed by Innovent with Lilly. In the 610-person GLORY-1 trial, published in the New England Journal of Medicine in May 2025, it produced 14.8% weight loss at 48 weeks on 6 mg against 0.5% on placebo; a 9 mg dose reached 16.7% at 60 weeks in the peer-reviewed GLORY-2 trial. China's regulator approved it for chronic weight management on 27 June 2025 and later for type 2 diabetes. It is not approved in the US, EU or UK.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"3 phase 3 RCTs","regulatory_status":"Approved in China only","molecule":{"formula":"C207H317N45O65","molecular_weight":"4476","cas":"2259884-03-0","pubchem_cid":167312357,"note":null},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, once weekly","half_life":"About a week or longer — reported as 7 to 45 days across doses in the phase 1b trial","licensed_regimen":null,"product":null,"source":{"title":"Ji L, et al. Safety and efficacy of the GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) in Chinese adults with overweight or obesity: a phase 1b trial. eClinicalMedicine 2022","url":"https://www.sciencedirect.com/science/article/pii/S2589537022004217"}},"outcomes":[{"outcome":"Body weight","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"2 phase 3 RCTs","evidence":"GLORY-1, 610 Chinese adults, 48 weeks: −12.0% (4 mg) and −14.8% (6 mg) versus −0.5% placebo; at least 5% loss in 73.5%, 82.8% and 11.5%. GLORY-2, 461 adults, 60 weeks on 9 mg: −16.65% versus −1.50%; 84.3% versus 33.1% lost at least 5%.","references":[{"citation":"Ji L, et al. Once-weekly mazdutide in Chinese adults with obesity or overweight (GLORY-1).","where":"N Engl J Med, 2025; DOI 10.1056/NEJMoa2411528","url":"https://pubmed.ncbi.nlm.nih.gov/40421736/"},{"citation":"Gao L, et al. Treatment with 9-mg mazdutide for weight reduction in Chinese adults with obesity: the GLORY-2 randomized clinical trial.","where":"JAMA, 2026;336:377–388","url":"https://pubmed.ncbi.nlm.nih.gov/42251595/"}],"verbatim":{"text":"At week 48, the mean percentage change in body weight from baseline was -11.00% (95% CI, -12.27 to -9.73) in the 4-mg mazdutide group, -14.01% (95% CI, -15.36 to -12.66) in the 6-mg mazdutide group, and 0.30% (95% CI, -0.98 to 1.58) in the placebo group, and 35.7%, 49.5%, and 2.0% of the participants, respectively, had a weight reduction of at least 15% (P<0.001 for all comparisons with placebo).","citation":"Ji L, et al. Once-weekly mazdutide in Chinese adults with obesity or overweight (GLORY-1).","url":"https://pubmed.ncbi.nlm.nih.gov/40421736/"}},{"outcome":"Liver fat","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"Phase 3 sub-analyses","evidence":"Among participants with baseline liver fat above 10%: −66% (4 mg) and −80% (6 mg) versus −5% in GLORY-1; −72% versus +5% in GLORY-2.","references":[{"citation":"Ji L, et al. Once-weekly mazdutide in Chinese adults with obesity or overweight (GLORY-1).","where":"N Engl J Med, 2025; DOI 10.1056/NEJMoa2411528","url":"https://pubmed.ncbi.nlm.nih.gov/40421736/"},{"citation":"Gao L, et al. Treatment with 9-mg mazdutide for weight reduction in Chinese adults with obesity: the GLORY-2 randomized clinical trial.","where":"JAMA, 2026;336:377–388","url":"https://pubmed.ncbi.nlm.nih.gov/42251595/"}]},{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"DREAMS phase 3 programme","evidence":"DREAMS-1 and DREAMS-2 in type 2 diabetes met their HbA1c endpoints; approved for glycaemic control in China on that basis. DREAMS-3 reported superiority to semaglutide on HbA1c and weight.","references":[{"citation":"Innovent. Mazdutide received approval from China's NMPA for chronic weight management; DREAMS programme in type 2 diabetes.","where":"Press releases, 2025","url":"https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-first-dual-gcgglp-1-receptor-agonist-received-approval-from-chinas-nmpa-for-chronic-weight-management-302493152.html"}]},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"Phase 3","evidence":"Nausea, diarrhoea and vomiting were the most frequent adverse events, mostly mild to moderate; discontinuation for adverse events 2.9% versus 0% in GLORY-2.","references":[{"citation":"Ji L, et al. Once-weekly mazdutide in Chinese adults with obesity or overweight (GLORY-1).","where":"N Engl J Med, 2025; DOI 10.1056/NEJMoa2411528","url":"https://pubmed.ncbi.nlm.nih.gov/40421736/"},{"citation":"Gao L, et al. Treatment with 9-mg mazdutide for weight reduction in Chinese adults with obesity: the GLORY-2 randomized clinical trial.","where":"JAMA, 2026;336:377–388","url":"https://pubmed.ncbi.nlm.nih.gov/42251595/"}]}],"regions":[{"region":"European Union","status":"Not authorised","note":"No EMA application. Products sold online as mazdutide are unauthorised medicines."},{"region":"United States","status":"Not approved; cannot be compounded","note":"Phase 2 in the US. The FDA has warned companies selling 'research' mazdutide for human use; it cannot be compounded."},{"region":"United Kingdom","status":"Unlicensed","note":"No MHRA licence; supply is an offence."},{"region":"Australia","status":"Unapproved","note":"Not on the ARTG; prescription-only substance with no lawful supply."},{"region":"Canada","status":"Not authorised","note":"No DIN."},{"region":"Sport (WADA)","status":"Not on the list","note":"Approved by China's NMPA, so S0 does not apply; not named in any section. Athletes should check the annual list."}],"faq":[{"q":"Is mazdutide approved?","a":"In China, yes — for chronic weight management since 27 June 2025 and for type 2 diabetes since later that year. Nowhere else. In the US, EU, UK, Australia and Canada it is an unapproved drug."},{"q":"How does mazdutide compare with tirzepatide?","a":"No head-to-head trial exists. GLORY-2's 16.7% at 60 weeks on 9 mg sits between semaglutide's and tirzepatide's own trial results, but cross-trial comparison is unreliable — different populations, durations and placebo responses."},{"q":"Can I buy mazdutide online?","a":"Not legally outside China, and the FDA has specifically named it in warning letters to research-chemical sellers. What arrives in a vial is unverified."}],"references":[{"cite":"Ji L, et al. Once-weekly mazdutide in Chinese adults with obesity or overweight (GLORY-1).","where":"N Engl J Med, 2025; DOI 10.1056/NEJMoa2411528","url":"https://pubmed.ncbi.nlm.nih.gov/40421736/","note":"610 adults, 48 weeks."},{"cite":"Gao L, et al. Treatment with 9-mg mazdutide for weight reduction in Chinese adults with obesity: the GLORY-2 randomized clinical trial.","where":"JAMA, 2026;336:377–388","url":"https://pubmed.ncbi.nlm.nih.gov/42251595/","note":"461 adults, 60 weeks on 9 mg; −16.65% versus −1.50%."},{"cite":"Innovent. Mazdutide received approval from China's NMPA for chronic weight management; DREAMS programme in type 2 diabetes.","where":"Press releases, 2025","url":"https://www.prnewswire.com/news-releases/innovent-announces-mazdutide-first-dual-gcgglp-1-receptor-agonist-received-approval-from-chinas-nmpa-for-chronic-weight-management-302493152.html","note":"Approval 27 June 2025."},{"cite":"Mazdutide: first approval.","where":"Drugs, 2025","url":"https://link.springer.com/article/10.1007/s40265-025-02249-y","note":"Regulatory summary."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication from GLORY-1 and GLORY-2 (both peer-reviewed) and the NMPA approvals."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"kisspeptin","name":"Kisspeptin","aliases":["kisspeptin-10","kisspeptin-54","metastin","KP-10","KP-54"],"url":"https://lyoresearch.com/compounds/kisspeptin","class":{"id":"reproductive-hormones","name":"Reproductive and neuroendocrine hormones","url":"https://lyoresearch.com/classes/reproductive-hormones"},"summary":"Kisspeptin is the hormone that switches on the reproductive axis: it makes the hypothalamus release GnRH, which drives LH, FSH and the sex hormones. In people it reliably raises LH within minutes, has been used as an egg-maturation trigger in IVF in phase 2 trials, and in two small randomised crossover trials at Imperial College London (32 women, 32 men) increased sexual-brain activation and reduced sexual aversion in people with low sexual desire. All of that is research-scale. It is not an approved medicine anywhere and is prohibited for male athletes.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"10+ small studies","regulatory_status":"Not approved","molecule":{"formula":"C63H83N17O14","molecular_weight":"1302.4","cas":"374675-21-5","pubchem_cid":25240297,"note":"Kisspeptin-10, the fragment used in human studies"},"pharmacokinetics":{"basis":"human","route":"Intravenous (healthy men)","half_life":"About 4 minutes (kisspeptin-10, intravenous); kisspeptin-54 about six times longer","licensed_regimen":null,"product":null,"source":{"title":"Jayasena CN, et al. Direct comparison of the effects of intravenous kisspeptin-10, kisspeptin-54 and GnRH on gonadotrophin secretion in healthy men. Hum Reprod 2015","url":"https://pubmed.ncbi.nlm.nih.gov/26089302/"}},"outcomes":[{"outcome":"LH and testosterone release","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"Many small studies","evidence":"Single doses of kisspeptin-10 or -54 raise LH within 30 minutes in healthy men and women — one of the most reproducible findings in human neuroendocrinology. Continuous exposure desensitises the response.","references":[{"citation":"Dhillo WS, et al. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males; and subsequent physiology studies from the same group.","where":"J Clin Endocrinol Metab, 2005 onward","url":"https://pubmed.ncbi.nlm.nih.gov/?term=kisspeptin+Dhillo+LH+humans"}]},{"outcome":"IVF egg maturation trigger","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"2 phase 2 trials","evidence":"Kisspeptin-54 as the final maturation trigger in 53 and then 60 women at high risk of ovarian hyperstimulation: live births achieved with no cases of severe OHSS. Not compared head-to-head with standard triggers at scale.","references":[{"citation":"Abbara A, et al. Efficacy of kisspeptin-54 to trigger oocyte maturation in women at high risk of OHSS during IVF therapy.","where":"J Clin Endocrinol Metab, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=kisspeptin-54+trigger+oocyte+maturation+OHSS+Abbara"}]},{"outcome":"Sexual desire (women with HSDD)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 crossover RCT (n=32)","evidence":"Two-visit double-blind crossover in 32 premenopausal women: kisspeptin infusion increased activation in sexual-processing brain regions on fMRI and reduced sexual aversion scores. A mechanism study, not a treatment trial.","references":[{"citation":"Thurston L, et al. Effects of kisspeptin administration in women with hypoactive sexual desire disorder: a randomized clinical trial.","where":"JAMA Netw Open, 2022; DOI 10.1001/jamanetworkopen.2022.36131","url":"https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797718"}],"verbatim":{"text":"Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P < .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02).","citation":"Thurston L, et al. Effects of kisspeptin administration in women with hypoactive sexual desire disorder: a randomized clinical trial.","url":"https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797718"}},{"outcome":"Sexual desire and arousal (men with HSDD)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 crossover RCT (n=32)","evidence":"Same design in 32 men: increased sexual-brain activation and a modest increase in penile tumescence to erotic stimuli. Single infusion; no data on repeated use.","references":[{"citation":"Mills EG, et al. Effects of kisspeptin on sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder: a randomized clinical trial.","where":"JAMA Netw Open, 2023; DOI 10.1001/jamanetworkopen.2022.54313","url":"https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800937"}],"verbatim":{"text":"On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003).","citation":"Mills EG, et al. Effects of kisspeptin on sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder: a randomized clinical trial.","url":"https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800937"}},{"outcome":"Safety","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":true,"human_studies":"Small studies","evidence":"No side effects reported in the HSDD trials; the fertility studies reported no severe OHSS. Nothing is known about repeated self-administration.","references":[{"citation":"Thurston L, et al. Effects of kisspeptin administration in women with hypoactive sexual desire disorder: a randomized clinical trial.","where":"JAMA Netw Open, 2022; DOI 10.1001/jamanetworkopen.2022.36131","url":"https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797718"},{"citation":"Mills EG, et al. Effects of kisspeptin on sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder: a randomized clinical trial.","where":"JAMA Netw Open, 2023; DOI 10.1001/jamanetworkopen.2022.54313","url":"https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800937"}]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation. Supplying it for human use is an offence under national medicines law."},{"region":"United States","status":"Not approved; compounding barred","note":"Kisspeptin-10 remains in Category 2 of the FDA's 503A list (significant safety risks) as of April 2026 — it may not be compounded."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Used only in academic trials; supply for human use is an offence."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG."},{"region":"Canada","status":"Not authorised","note":"No DIN; selling it is illegal."},{"region":"Sport (WADA)","status":"Prohibited at all times (males)","note":"S2.2.1: 'kisspeptin and its agonist analogues', prohibited in males as an LH/testosterone releaser."}],"faq":[{"q":"Does kisspeptin increase testosterone?","a":"Acutely, yes: a single dose reliably raises LH and then testosterone in men within an hour or two. Repeated or continuous exposure desensitises the axis and can lower it. That acute effect is why it is banned for male athletes."},{"q":"Is kisspeptin a treatment for low libido?","a":"Not yet. Two single-dose crossover trials in 32 women and 32 men showed increased sexual-brain activation and reduced sexual aversion. They were designed to test a mechanism, not to treat anyone, and no trial has tested weeks of use."},{"q":"Is kisspeptin used in IVF?","a":"In research. Phase 2 trials used kisspeptin-54 as the trigger for final egg maturation in women at high risk of ovarian hyperstimulation, with live births and no severe OHSS. It is not a standard-of-care trigger."}],"references":[{"cite":"Dhillo WS, et al. Kisspeptin-54 stimulates the hypothalamic-pituitary gonadal axis in human males; and subsequent physiology studies from the same group.","where":"J Clin Endocrinol Metab, 2005 onward","url":"https://pubmed.ncbi.nlm.nih.gov/?term=kisspeptin+Dhillo+LH+humans","note":"The foundational human dosing studies."},{"cite":"Abbara A, et al. Efficacy of kisspeptin-54 to trigger oocyte maturation in women at high risk of OHSS during IVF therapy.","where":"J Clin Endocrinol Metab, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=kisspeptin-54+trigger+oocyte+maturation+OHSS+Abbara","note":"Phase 2; follows Jayasena 2014 (n=53)."},{"cite":"Thurston L, et al. Effects of kisspeptin administration in women with hypoactive sexual desire disorder: a randomized clinical trial.","where":"JAMA Netw Open, 2022; DOI 10.1001/jamanetworkopen.2022.36131","url":"https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2797718","note":"32 premenopausal women, double-blind crossover."},{"cite":"Mills EG, et al. Effects of kisspeptin on sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder: a randomized clinical trial.","where":"JAMA Netw Open, 2023; DOI 10.1001/jamanetworkopen.2022.54313","url":"https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2800937","note":"32 men, double-blind crossover."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication from the Imperial College physiology, IVF and HSDD trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"thymosin-alpha-1","name":"Thymosin α1","aliases":["thymalfasin","Zadaxin","Tα1","thymosin alpha 1"],"url":"https://lyoresearch.com/compounds/thymosin-alpha-1","class":{"id":"immune-peptides","name":"Immune, antimicrobial and repair-signal peptides","url":"https://lyoresearch.com/classes/immune-peptides"},"summary":"Thymosin α1 is a 28-amino-acid peptide from the thymus that nudges T-cells and dendritic cells toward a stronger antiviral response. It has been sold as Zadaxin for hepatitis B and as an immune adjunct in China, Italy and some thirty other countries since the 1990s, but the largest trial ever run on it — 1,106 adults with sepsis, published in the BMJ in January 2025 — found no reduction in 28-day mortality (23.4% versus 24.1%). It is not approved in the US, EU-wide or UK.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"20+ RCTs","regulatory_status":"Approved outside US/EU (Zadaxin)","molecule":{"formula":"C129H215N33O55","molecular_weight":"3108.3","cas":"62304-98-7","pubchem_cid":16130571,"note":null},"pharmacokinetics":{"basis":"human","route":"Subcutaneous","half_life":"Less than 3 hours (subcutaneous, healthy volunteers)","licensed_regimen":null,"product":null,"source":{"title":"Pharmacokinetics of thymosin alpha1 after subcutaneous injection of three different formulations in healthy volunteers. Int J Clin Pharmacol Ther 1999","url":"https://pubmed.ncbi.nlm.nih.gov/10027483/"}},"outcomes":[{"outcome":"Sepsis mortality","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"1 large phase 3 RCT + earlier smaller RCTs","evidence":"TESTS, 1,106 adults in 22 Chinese ICUs, twice-daily injections for 7 days: 28-day mortality 23.4% versus 24.1% on placebo (hazard ratio 0.99, 95% CI 0.77–1.27). No secondary or safety outcome differed. Earlier smaller trials that suggested benefit are superseded.","references":[{"citation":"Wu J, et al. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.","where":"BMJ, 2025; 388:e082583","url":"https://pubmed.ncbi.nlm.nih.gov/39814420/"}],"verbatim":{"text":"28 day all cause mortality occurred in 127 participants (23.4%) in the thymosin α1 group and 132 (24.1%) in the placebo group (hazard ratio 0.99, 95% confidence interval 0.77 to 1.27; P=0.93 with log-rank test).","citation":"Wu J, et al. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/39814420/"}},{"outcome":"Chronic hepatitis B (viral response)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":false,"human_studies":"10+ RCTs, mostly small","evidence":"Trials from the 1990s–2000s show modest increases in sustained response, alone or with interferon; heterogeneous quality. The basis for the Zadaxin approvals.","references":[{"citation":"Thymalfasin (Zadaxin) clinical overview: hepatitis B and vaccine-adjuvant randomised trials.","where":"Multiple journals, 1996–2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=thymalfasin+randomized+hepatitis+B"}]},{"outcome":"Vaccine response in the elderly and dialysis patients","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":false,"human_studies":"Several RCTs","evidence":"Improved seroconversion to influenza and hepatitis B vaccines in older adults and haemodialysis patients in randomised studies; effect sizes moderate, trials small.","references":[{"citation":"Thymalfasin (Zadaxin) clinical overview: hepatitis B and vaccine-adjuvant randomised trials.","where":"Multiple journals, 1996–2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=thymalfasin+randomized+hepatitis+B"}]},{"outcome":"COVID-19 outcomes","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Observational + small RCTs","evidence":"Chinese observational cohorts and small randomised studies reported lower mortality in severe COVID-19; confounded and never confirmed in a large trial.","references":[{"citation":"Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials.","where":"Front Cell Infect Microbiol, 2025","url":"https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1673959/full"}]},{"outcome":"Safety","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":true,"human_studies":"TESTS + decades of use","evidence":"Injection-site reactions; no signal for serious harm in TESTS or in long clinical use. Subgroup findings in TESTS (worse in under-60s, better in diabetics) are hypothesis-generating only.","references":[{"citation":"Wu J, et al. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.","where":"BMJ, 2025; 388:e082583","url":"https://pubmed.ncbi.nlm.nih.gov/39814420/"}]}],"regions":[{"region":"European Union","status":"Authorised in Italy only","note":"Zadaxin is nationally authorised in Italy; no EU-wide marketing authorisation. Elsewhere in the EU it is an unauthorised medicine."},{"region":"United States","status":"Not approved; compounding withdrawn","note":"Orphan designations but no approval. Its 503A compounding nomination is listed as withdrawn (April 2026)."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence; unlicensed medicine when supplied for human use."},{"region":"Australia","status":"Not registered","note":"Not on the ARTG; prescription-only substance."},{"region":"Canada","status":"Not authorised","note":"No DIN."},{"region":"Sport (WADA)","status":"Not on the list","note":"Approved in several countries, so S0 does not apply; not named in any section."}],"faq":[{"q":"Is thymosin alpha 1 approved?","a":"In China, Italy and roughly thirty other countries, yes, as Zadaxin for hepatitis B and as an immune adjunct. Not in the US, not EU-wide, not in the UK, Australia or Canada."},{"q":"Does thymosin alpha 1 help in sepsis?","a":"The best evidence says no. TESTS, a 1,106-person double-blind phase 3 trial published in the BMJ in 2025, found 28-day mortality of 23.4% with the drug and 24.1% with placebo. Earlier meta-analyses suggesting benefit rested on smaller trials."},{"q":"Is it the same as TB-500?","a":"No. Thymosin α1 and thymosin β4 are different peptides with different biology. TB-500 is a fragment of thymosin β4, has no approvals anywhere, and is prohibited in sport; thymosin α1 is an approved immune drug in several countries and not on the WADA list."}],"references":[{"cite":"Wu J, et al. The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.","where":"BMJ, 2025; 388:e082583","url":"https://pubmed.ncbi.nlm.nih.gov/39814420/","note":"1,106 adults; 28-day mortality 23.4% vs 24.1%."},{"cite":"Thymalfasin (Zadaxin) clinical overview: hepatitis B and vaccine-adjuvant randomised trials.","where":"Multiple journals, 1996–2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=thymalfasin+randomized+hepatitis+B","note":"Heterogeneous, mostly small RCTs."},{"cite":"Efficacy of thymosin α1 for sepsis: a systematic review and meta-analysis of randomized controlled trials.","where":"Front Cell Infect Microbiol, 2025","url":"https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1673959/full","note":"Includes TESTS; earlier pooled estimates were driven by small trials."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication, led by the TESTS trial."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"ll-37","name":"LL-37","aliases":["cathelicidin","hCAP18 fragment","antimicrobial peptide"],"url":"https://lyoresearch.com/compounds/ll-37","class":{"id":"immune-peptides","name":"Immune, antimicrobial and repair-signal peptides","url":"https://lyoresearch.com/classes/immune-peptides"},"summary":"LL-37 is the only cathelicidin peptide humans make — a 37-amino-acid antimicrobial produced by skin, gut and immune cells that kills bacteria and signals inflammation and repair. The human evidence is two randomised trials of a topical gel on venous leg ulcers: a 34-patient phase 2a that found faster healing, and a 148-patient phase 2b that did not, except in a subgroup of large wounds. Nothing supports the injected 'immune' or 'anti-inflammatory' uses sold online, and injected LL-37 is pro-inflammatory in the laboratory.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"2 RCTs (topical)","regulatory_status":"Not approved","molecule":{"formula":"C205H340N60O53","molecular_weight":"4493","cas":"154947-66-7","pubchem_cid":16198951,"note":null},"pharmacokinetics":{"basis":"none","route":"Topical in the trials; injected as sold with no human study","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Venous leg ulcer healing (topical)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"2 RCTs (n=34, n=148)","evidence":"Phase 2a (2014): 34 patients, healing rate roughly six-fold faster at 0.5 mg/ml than placebo over 4 weeks. Phase 2b (2021): 148 patients, 13 weeks; complete closure 26.5% and 24.7% versus 25.3% on placebo — no difference overall, a significant benefit only in ulcers of 10 cm² or more (28.1% versus 8.1%).","references":[{"citation":"Grönberg A, et al. Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial.","where":"Wound Repair Regen, 2014; DOI 10.1111/wrr.12211","url":"https://pubmed.ncbi.nlm.nih.gov/25041740/"},{"citation":"Mahlapuu M, et al. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial.","where":"Wound Repair Regen, 2021","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9298190/"}],"verbatim":{"text":"The healing rate constants for 0.5 and 1.6 mg/mL of LL-37 were approximately six- and threefold higher than for placebo (p = 0.003 for 0.5 mg/mL and p = 0.088 for 1.6 mg/mL).","citation":"Grönberg A, et al. Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial.","url":"https://pubmed.ncbi.nlm.nih.gov/25041740/"}},{"outcome":"Antimicrobial action in people","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Kills bacteria in vitro and in animal models; no human trial has tested LL-37 as an anti-infective in any route.","references":[{"citation":"Reviews of LL-37 biology in infection, wound repair and autoimmunity.","where":"Various","url":"https://pubmed.ncbi.nlm.nih.gov/?term=LL-37+cathelicidin+review+psoriasis+inflammation"}]},{"outcome":"Systemic 'immune support' or anti-inflammatory use","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0","evidence":"No human data by injection at all. In cells and mice LL-37 is a driver of inflammation in psoriasis and lupus, which argues against, not for, the marketed use.","references":[{"citation":"Reviews of LL-37 biology in infection, wound repair and autoimmunity.","where":"Various","url":"https://pubmed.ncbi.nlm.nih.gov/?term=LL-37+cathelicidin+review+psoriasis+inflammation"}]},{"outcome":"Safety (topical)","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":true,"human_studies":"2 RCTs","evidence":"Topical gel well tolerated in both trials; serious adverse events in 7.4% of the phase 2b population, none attributed to the drug. Nothing is known about injected use.","references":[{"citation":"Mahlapuu M, et al. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial.","where":"Wound Repair Regen, 2021","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9298190/"}]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation. Supplying it for human use is an offence under national medicines law."},{"region":"United States","status":"Not approved; compounding withdrawn","note":"Its 503A nomination (cathelicidin LL-37) is listed as withdrawn since April 2026; it was not among the peptides the advisory committee reviewed in July 2026."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Selling or supplying it for human use is an offence."},{"region":"Australia","status":"Schedule 4, unapproved","note":"Prescription-only substance not on the ARTG."},{"region":"Canada","status":"Not authorised","note":"No DIN; selling it is illegal."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so it falls under S0 (non-approved substances)."}],"faq":[{"q":"Does LL-37 heal wounds?","a":"In the larger of two randomised trials, no better than placebo overall: complete closure in about a quarter of patients in every group after 13 weeks. Large ulcers did better on the low dose in a subgroup analysis. The small earlier trial was positive."},{"q":"Is LL-37 an antibiotic?","a":"In the test tube, yes — it is part of the body's own antimicrobial defence. No human trial has tested it as an anti-infective, and it degrades quickly in blood."},{"q":"Is injected LL-37 anti-inflammatory?","a":"The laboratory evidence points the other way: LL-37 drives inflammation in psoriasis and lupus models. There are no human data for injected use in any condition."}],"references":[{"cite":"Grönberg A, et al. Treatment with LL-37 is safe and effective in enhancing healing of hard-to-heal venous leg ulcers: a randomized, placebo-controlled clinical trial.","where":"Wound Repair Regen, 2014; DOI 10.1111/wrr.12211","url":"https://pubmed.ncbi.nlm.nih.gov/25041740/","note":"34 patients, phase 1/2a."},{"cite":"Mahlapuu M, et al. Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: a multicentric prospective randomized placebo-controlled clinical trial.","where":"Wound Repair Regen, 2021","url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC9298190/","note":"148 patients, phase 2b; primary endpoint not met."},{"cite":"Reviews of LL-37 biology in infection, wound repair and autoimmunity.","where":"Various","url":"https://pubmed.ncbi.nlm.nih.gov/?term=LL-37+cathelicidin+review+psoriasis+inflammation","note":"Preclinical mechanism; no systemic human data."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication from the two topical wound-healing trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"ss-31","name":"SS-31 (elamipretide)","aliases":["elamipretide","MTP-131","Bendavia","Forzinity","Elamipretide HCl","D-Arg-Dmt-Lys-Phe-NH2"],"url":"https://lyoresearch.com/compounds/ss-31","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"SS-31, developed as elamipretide, is a four-amino-acid peptide that concentrates in mitochondria and binds cardiolipin, a lipid of the inner membrane. After a decade of trials it was approved in the United States in September 2025 for Barth syndrome, an ultra-rare genetic disease — on the strength of an open-label extension, since its randomised crossover missed both primary endpoints. Larger randomised trials in primary mitochondrial myopathy and in heart failure were negative. It is a genuine, narrowly approved medicine, not a general 'mitochondrial' or anti-ageing treatment.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Several RCTs (mostly negative) + one approval","regulatory_status":"Approved (Rx, US; Barth syndrome only)","molecule":{"formula":"C32H49N9O5","molecular_weight":"639.8","cas":"736992-21-5","pubchem_cid":11764719,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, once daily","half_life":"Not stated in the label","licensed_regimen":"40 mg subcutaneously once daily in patients weighing at least 30 kg (Barth syndrome)","product":"Forzinity (elamipretide)","source":{"title":"Forzinity prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=146bf34c-76f2-48db-ac07-fb29cce2cd75"}},"outcomes":[{"outcome":"Barth syndrome (muscle strength & symptoms)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 crossover RCT + open-label extension (n=12)","evidence":"TAZPOWER: the 12-week randomised crossover missed both primary endpoints; improvements in walk distance and symptom score emerged only in the open-label extension at 36 weeks. This extension is the basis of the 2025 accelerated approval.","references":[{"citation":"Thompson WR, et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate elamipretide in Barth syndrome (TAZPOWER).","where":"Genet Med, 2021;23:471–478","url":"https://pubmed.ncbi.nlm.nih.gov/33077895/"}],"verbatim":{"text":"In part 1 neither primary endpoint was met. At 36 weeks in part 2, there were significant improvements in 6MWT (+95.9 m, p = 0.024) and BTHS-SA (-2.1 points, p = 0.031).","citation":"Thompson WR, et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate elamipretide in Barth syndrome (TAZPOWER).","url":"https://pubmed.ncbi.nlm.nih.gov/33077895/"}},{"outcome":"Primary mitochondrial myopathy","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 phase 3 RCT (n=218)","evidence":"MMPOWER-3, the pivotal trial in the larger primary-mitochondrial-myopathy population, was negative on both primary endpoints at 24 weeks.","references":[{"citation":"Karaa A, et al. Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial.","where":"Neurology, 2023;101:e238–e252","url":"https://pubmed.ncbi.nlm.nih.gov/37268435/"}],"verbatim":{"text":"The study did not meet its primary endpoints assessing changes in the 6MWT and PMMSA total fatigue score (TFS).","citation":"Karaa A, et al. Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial.","url":"https://pubmed.ncbi.nlm.nih.gov/37268435/"}},{"outcome":"Heart failure (reduced ejection fraction)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 phase 2 RCT (n=71)","evidence":"PROGRESS-HF tested four weeks of daily elamipretide against placebo and found no improvement in left-ventricular end-systolic volume.","references":[{"citation":"Butler J, et al. Effects of elamipretide on left ventricular function in patients with HFrEF: the PROGRESS-HF phase 2 trial.","where":"J Card Fail, 2020;26:429–437","url":"https://pubmed.ncbi.nlm.nih.gov/32068002/"}],"verbatim":{"text":"Elamipretide was well tolerated but did not improve LVESV at 4 weeks in patients with stable HFrEF compared with placebo.","citation":"Butler J, et al. Effects of elamipretide on left ventricular function in patients with HFrEF: the PROGRESS-HF phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/32068002/"}},{"outcome":"Dry age-related macular degeneration","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 phase 2 RCT (n=176)","evidence":"ReCLAIM-2 missed its two primary endpoints; a slowing of ellipsoid-zone loss on OCT is a secondary signal the developer is carrying into phase 3.","references":[{"citation":"Ehlers JP, et al. ReCLAIM-2: a randomized phase 2 clinical trial evaluating elamipretide in dry age-related macular degeneration.","where":"Ophthalmol Sci, 2025;5:100628","url":"https://pubmed.ncbi.nlm.nih.gov/39605874/"}],"verbatim":{"text":"While the primary end points were not met in this phase II study, elamipretide treatment was associated with a slowing of progressive EZ degradation/loss, a surrogate for photoreceptor damage.","citation":"Ehlers JP, et al. ReCLAIM-2: a randomized phase 2 clinical trial evaluating elamipretide in dry age-related macular degeneration.","url":"https://pubmed.ncbi.nlm.nih.gov/39605874/"}},{"outcome":"Safety in humans","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":true,"human_studies":"Across the trial programme","evidence":"Consistently well tolerated across trials; the main issue is injection-site reactions. Long-term safety data come mostly from the small Barth open-label extension.","references":[{"citation":"Karaa A, et al. Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial.","where":"Neurology, 2023;101:e238–e252","url":"https://pubmed.ncbi.nlm.nih.gov/37268435/"}],"verbatim":{"text":"Elamipretide treatment was well-tolerated with most adverse events being mild to moderate in severity.","citation":"Karaa A, et al. Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial.","url":"https://pubmed.ncbi.nlm.nih.gov/37268435/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"No EMA marketing authorisation. Supplying it for human use is an offence under national medicines law."},{"region":"United States","status":"Approved (Barth syndrome only)","note":"Accelerated approval September 2025 as Forzinity (elamipretide) for Barth syndrome. Any other use, and any product sold as 'SS-31' outside that channel, is unapproved."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence. Sold otherwise as an unlicensed medicine or research chemical."},{"region":"Australia","status":"Not on the ARTG","note":"Prescription-only, unapproved; imports without a prescription are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Not listed","note":"Not named on the 2026 Prohibited List; athletes should still check, since new peptides are added regularly."}],"faq":[{"q":"Is SS-31 approved?","a":"Only for one disease. In September 2025 the US FDA approved elamipretide (Forzinity) for Barth syndrome, an ultra-rare genetic disorder. It is not approved for heart failure, general fatigue, ageing or 'mitochondrial health', and the trials in the larger conditions were negative."},{"q":"Is SS-31 the same as elamipretide?","a":"Yes. SS-31 is the research name; elamipretide is the drug name; MTP-131 and Bendavia are older codes for the same molecule."},{"q":"Does it help with ageing or energy?","a":"There is no human evidence for that. Its record in people is one narrow approval and several failed trials in serious diseases."}],"references":[{"cite":"Thompson WR, et al. A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate elamipretide in Barth syndrome (TAZPOWER).","where":"Genet Med, 2021;23:471–478","url":"https://pubmed.ncbi.nlm.nih.gov/33077895/","note":"12 subjects; part-1 crossover negative, part-2 extension positive at 36 weeks."},{"cite":"Karaa A, et al. Efficacy and safety of elamipretide in individuals with primary mitochondrial myopathy: the MMPOWER-3 randomized clinical trial.","where":"Neurology, 2023;101:e238–e252","url":"https://pubmed.ncbi.nlm.nih.gov/37268435/","note":"218 participants; both primary endpoints negative."},{"cite":"Butler J, et al. Effects of elamipretide on left ventricular function in patients with HFrEF: the PROGRESS-HF phase 2 trial.","where":"J Card Fail, 2020;26:429–437","url":"https://pubmed.ncbi.nlm.nih.gov/32068002/","note":"71 patients; no effect on LVESV."},{"cite":"Ehlers JP, et al. ReCLAIM-2: a randomized phase 2 clinical trial evaluating elamipretide in dry age-related macular degeneration.","where":"Ophthalmol Sci, 2025;5:100628","url":"https://pubmed.ncbi.nlm.nih.gov/39605874/","note":"176 patients; primaries missed, ellipsoid-zone secondary signal."},{"cite":"US FDA / Stealth BioTherapeutics. Accelerated approval of Forzinity (elamipretide) for Barth syndrome.","where":"FDA, September 2025","url":"https://www.fda.gov/drugs","note":"First therapy approved for Barth syndrome; accelerated approval."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Grades reflect one accelerated approval and several negative randomised trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"oxytocin","name":"Oxytocin (intranasal)","aliases":["Pitocin","Syntocinon","the bonding hormone","intranasal oxytocin"],"url":"https://lyoresearch.com/compounds/oxytocin","class":{"id":"reproductive-hormones","name":"Reproductive and neuroendocrine hormones","url":"https://lyoresearch.com/classes/reproductive-hormones"},"summary":"Oxytocin is a natural nine-amino-acid hormone, licensed for decades as an injection to induce labour and control bleeding. The compound sold and discussed in the peptide world is intranasal oxytocin, promoted for bonding, appetite and social behaviour. Here the evidence is largely negative: the largest randomised trial in autism found no benefit, and a randomised obesity trial found no weight loss. It is well tolerated, but the popular claims rest on small early studies that the big trials did not confirm.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Many RCTs (intranasal mostly null)","regulatory_status":"Approved (Rx) as injection; intranasal use unlicensed","molecule":{"formula":"C43H66N12O12S2","molecular_weight":"1007.2","cas":"50-56-6","pubchem_cid":439302,"note":null},"pharmacokinetics":{"basis":"label","route":"Intravenous infusion (labour) or intramuscular injection (postpartum)","half_life":"About 1-6 minutes","licensed_regimen":"Labour induction: IV infusion 0.5-1 mU/min initially, increased by 1-2 mU/min every 30-60 min; postpartum: 10-40 units IV infusion or 10 units IM","product":"Pitocin","source":{"title":"Pitocin prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=969d5b35-0add-4c23-9605-6a5b6ab65c95"}},"outcomes":[{"outcome":"Social function in autism","grade":"B","grade_meaning":"probable, not settled","effect_size":"not measurable","adverse":false,"human_studies":"1 large phase 2 RCT (n=290)","evidence":"SOARS-B, the definitive 24-week trial in children and adolescents, found no difference from placebo on its primary social-withdrawal measure or on secondary outcomes.","references":[{"citation":"Sikich L, et al. Intranasal oxytocin in children and adolescents with autism spectrum disorder (SOARS-B).","where":"N Engl J Med, 2021;385:1462–1473","url":"https://pubmed.ncbi.nlm.nih.gov/34644471/"}],"verbatim":{"text":"The least-squares mean change from baseline in the ABC-mSW score (primary outcome) was -3.7 in the oxytocin group and -3.5 in the placebo group (least-squares mean difference, -0.2; 95% confidence interval, -1.5 to 1.0; P = 0.61).","citation":"Sikich L, et al. Intranasal oxytocin in children and adolescents with autism spectrum disorder (SOARS-B).","url":"https://pubmed.ncbi.nlm.nih.gov/34644471/"}},{"outcome":"Weight loss in obesity","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 RCT (n=61)","evidence":"Eight weeks of intranasal oxytocin four times daily produced no weight change versus placebo, though it modestly reduced intake at a single test meal.","references":[{"citation":"Plessow F, et al. Intranasal oxytocin for obesity.","where":"NEJM Evidence, 2024;3:EVIDoa2300349","url":"https://pubmed.ncbi.nlm.nih.gov/38815173/"}],"verbatim":{"text":"There was no difference in body weight change from baseline to week 8 between oxytocin and placebo groups (0.20 vs. 0.26 kg; P=0.934).","citation":"Plessow F, et al. Intranasal oxytocin for obesity.","url":"https://pubmed.ncbi.nlm.nih.gov/38815173/"}},{"outcome":"Appetite / caloric intake (acute)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Small crossover studies","evidence":"A single dose lowered food intake at a laboratory test meal in the obesity trial and in earlier crossover work — an acute effect that did not translate into weight change over eight weeks.","references":[{"citation":"Plessow F, et al. Intranasal oxytocin for obesity.","where":"NEJM Evidence, 2024;3:EVIDoa2300349","url":"https://pubmed.ncbi.nlm.nih.gov/38815173/"}],"verbatim":{"text":"Oxytocin compared with placebo was associated with reduced caloric intake at the test meal (-31.4 vs. 120.6 kcal; difference [95% confidence interval], -152.0 kcal [-302.3 to -1.7]).","citation":"Plessow F, et al. Intranasal oxytocin for obesity.","url":"https://pubmed.ncbi.nlm.nih.gov/38815173/"}},{"outcome":"Safety (intranasal, short-term)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"Multiple RCTs","evidence":"Short-term intranasal use is well tolerated, with adverse events similar to placebo in the large trials. Long-term safety of daily self-dosing is not established.","references":[{"citation":"Sikich L, et al. Intranasal oxytocin in children and adolescents with autism spectrum disorder (SOARS-B).","where":"N Engl J Med, 2021;385:1462–1473","url":"https://pubmed.ncbi.nlm.nih.gov/34644471/"}],"verbatim":{"text":"The incidence and severity of adverse events were similar in the two groups.","citation":"Sikich L, et al. Intranasal oxytocin in children and adolescents with autism spectrum disorder (SOARS-B).","url":"https://pubmed.ncbi.nlm.nih.gov/34644471/"}}],"regions":[{"region":"European Union","status":"Approved as injection; nasal use unlicensed","note":"Oxytocin injection is authorised across the EU for obstetric use. A nasal spray (Syntocinon) was historically used for breastfeeding; general 'bonding' or weight use is off-label or unlicensed."},{"region":"United States","status":"Approved as injection (Pitocin)","note":"The injection is FDA-approved for obstetric indications. Intranasal oxytocin is not FDA-approved and is sold via compounding pharmacies and the grey market."},{"region":"United Kingdom","status":"Licensed as injection","note":"Syntocinon injection is MHRA-licensed for obstetric use; other routes and indications are unlicensed."},{"region":"Australia","status":"Registered as injection","note":"Injectable oxytocin is on the ARTG for obstetric use; intranasal products are not registered for the marketed 'wellness' uses."},{"region":"Canada","status":"Authorised as injection","note":"Injectable oxytocin carries a DIN; nasal 'wellness' products do not."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the 2026 Prohibited List."}],"faq":[{"q":"Does oxytocin nasal spray help autism?","a":"The largest randomised trial (SOARS-B, 290 children and adolescents over 24 weeks) found no benefit over placebo on social function. Earlier small studies had been more encouraging; the definitive trial was not."},{"q":"Will oxytocin help me lose weight?","a":"In a randomised trial, eight weeks of intranasal oxytocin produced no weight change versus placebo. It reduced intake at a single test meal, which did not translate into weight loss."},{"q":"Is the injection different from the spray?","a":"Yes. Injectable oxytocin is licensed obstetric medicine. The nasal spray sold for bonding and appetite is a different route and dose, and its marketed uses are largely unsupported by the big trials."}],"references":[{"cite":"Sikich L, et al. Intranasal oxytocin in children and adolescents with autism spectrum disorder (SOARS-B).","where":"N Engl J Med, 2021;385:1462–1473","url":"https://pubmed.ncbi.nlm.nih.gov/34644471/","note":"290 participants, 24 weeks; primary and secondary outcomes null."},{"cite":"Plessow F, et al. Intranasal oxytocin for obesity.","where":"NEJM Evidence, 2024;3:EVIDoa2300349","url":"https://pubmed.ncbi.nlm.nih.gov/38815173/","note":"61 adults, 8 weeks; no weight change, reduced single-meal intake."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Grades reflect large, well-conducted but mostly null intranasal trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"melanotan-2","name":"Melanotan II","aliases":["MT-II","MT-2","melanotan 2","cyclic α-MSH analogue"],"url":"https://lyoresearch.com/compounds/melanotan-2","class":{"id":"melanocortins","name":"Melanocortin agonists","url":"https://lyoresearch.com/classes/melanocortins"},"summary":"Melanotan II is a synthetic cyclic peptide that mimics α-melanocyte-stimulating hormone. Small early trials in the 1990s showed it darkens skin and, separately, triggers erections in men — the two effects it is still sold for. It has never completed later-stage trials and is not approved anywhere. Reported harms include nausea, uncontrolled erections, darkening and change of moles, and case reports of serious events such as kidney infarction, which is why regulators warn against it.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Small early-phase trials","regulatory_status":"Not approved","molecule":{"formula":"C50H69N15O9","molecular_weight":"1024.2","cas":"121062-08-6","pubchem_cid":92432,"note":null},"pharmacokinetics":{"basis":"none","route":"Subcutaneous in the 1996 pilot study, which reports no PK","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":{"title":"Dorr RT, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide, in a pilot phase-I clinical study. Life Sci 1996","url":"https://pubmed.ncbi.nlm.nih.gov/8637402/"}},"outcomes":[{"outcome":"Erectile function (psychogenic ED)","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"Small crossover RCTs","evidence":"In a 10-man double-blind crossover, Melanotan II produced clinically apparent erections in most treated men, far exceeding placebo — small, early, never taken to phase 3.","references":[{"citation":"Wessells H, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: a double-blind, placebo-controlled crossover study.","where":"J Urol, 1998;160:389–393","url":"https://pubmed.ncbi.nlm.nih.gov/9679884/"}],"verbatim":{"text":"Mean duration of tip rigidity greater than 80% was 38.0 minutes with Melanotan-II and 3.0 with placebo (p=0.0045).","citation":"Wessells H, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: a double-blind, placebo-controlled crossover study.","url":"https://pubmed.ncbi.nlm.nih.gov/9679884/"}},{"outcome":"Skin tanning","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"Pilot studies (n≈3–12)","evidence":"A pilot phase 1 study showed measurable tanning from a few low subcutaneous doses. The related peptide melanotan-1 (afamelanotide) went on to be developed properly and approved for a rare photosensitivity disorder; melanotan II did not.","references":[{"citation":"Dorr RT, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide, in a pilot phase-1 clinical study.","where":"Life Sci, 1996;58:1777–1784","url":"https://pubmed.ncbi.nlm.nih.gov/8637402/"}],"verbatim":{"text":"These results demonstrate that MT-II has tanning activity in humans given only 5 low doses every other day by subcutaneous injection.","citation":"Dorr RT, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide, in a pilot phase-1 clinical study.","url":"https://pubmed.ncbi.nlm.nih.gov/8637402/"}},{"outcome":"Safety in humans","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":true,"human_studies":"Trials + case reports","evidence":"Nausea, flushing, spontaneous erections and darkening of moles are common; case reports describe rhabdomyolysis and kidney infarction, and dermatologists warn that new or changing moles can mask melanoma. No systematic long-term safety data exist.","references":[{"citation":"Wessells H, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: a double-blind, placebo-controlled crossover study.","where":"J Urol, 1998;160:389–393","url":"https://pubmed.ncbi.nlm.nih.gov/9679884/"},{"citation":"Case reports of serious harm with melanotan II (e.g. renal infarction).","where":"CEN Case Rep and others, 2020","url":"https://pubmed.ncbi.nlm.nih.gov/31953620/"}]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation. National regulators (including in the UK and Nordic countries) have repeatedly warned against injectable melanotan sold online."},{"region":"United States","status":"Not approved","note":"Not approved by the FDA, which has warned consumers about melanotan products sold for tanning. The properly developed sibling, afamelanotide (Scenesse), is approved for a rare photosensitivity disorder — melanotan II is not."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it for human use is an offence under the Human Medicines Regulations 2012."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG. Supply without a prescription is unlawful; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it for human use is illegal."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not specifically named on the 2026 WADA Prohibited List, though as a non-approved substance it may fall under S0; athletes should verify."}],"faq":[{"q":"Does Melanotan II actually work for tanning?","a":"Small studies show it does darken skin. That is not the issue — the issue is that it is unapproved, non-selective, and the same activity changes moles and causes nausea and other effects, with no long-term safety data."},{"q":"Is it the same as the approved 'Scenesse'?","a":"No. Scenesse (afamelanotide) is a related but different, properly developed and approved peptide for a rare light-sensitivity disease. Melanotan II is the unapproved grey-market version."},{"q":"Why do regulators warn about it?","a":"Because it is injected without oversight, causes nausea, flushing and spontaneous erections, darkens and changes moles in a way that can hide melanoma, and has case reports of serious harm including kidney infarction."}],"references":[{"cite":"Wessells H, et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: a double-blind, placebo-controlled crossover study.","where":"J Urol, 1998;160:389–393","url":"https://pubmed.ncbi.nlm.nih.gov/9679884/","note":"10 men, crossover; the erection data."},{"cite":"Dorr RT, et al. Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide, in a pilot phase-1 clinical study.","where":"Life Sci, 1996;58:1777–1784","url":"https://pubmed.ncbi.nlm.nih.gov/8637402/","note":"3 volunteers; the tanning data."},{"cite":"Case reports of serious harm with melanotan II (e.g. renal infarction).","where":"CEN Case Rep and others, 2020","url":"https://pubmed.ncbi.nlm.nih.gov/31953620/","note":"Illustrative of the unmonitored-use risk."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Grade C — real small-trial efficacy, unquantified real-world harm."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"hexarelin","name":"Hexarelin","aliases":["examorelin","EP-23905","GH-releasing peptide"],"url":"https://lyoresearch.com/compounds/hexarelin","class":{"id":"gh-secretagogues","name":"GH secretagogues (GHRPs)","url":"https://lyoresearch.com/classes/gh-secretagogues"},"summary":"Hexarelin is a synthetic six-amino-acid growth-hormone-releasing peptide. Single doses cause a strong, well-documented growth-hormone spike in humans, but the one study of continued use showed the response fades within weeks and that IGF-1 and body composition did not meaningfully change. It was never developed into an approved medicine, and the muscle, fat-loss and cardiac claims made for it have no controlled human evidence.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Early-phase human studies","regulatory_status":"Not approved","molecule":{"formula":"C47H58N12O6","molecular_weight":"887.0","cas":"140703-51-1","pubchem_cid":6918297,"note":null},"pharmacokinetics":{"basis":"animal","route":"Intravenous in human GH-response studies, which report no PK","half_life":"No human pharmacokinetic data. Dog intravenous terminal half-life about 2 hours","licensed_regimen":null,"product":null,"source":{"title":"Roumi M, et al. Radioimmunoassay for hexarelin and its pharmacokinetic studies. Peptides 1995;16","url":"https://pubmed.ncbi.nlm.nih.gov/8545255/"}},"outcomes":[{"outcome":"Growth hormone release","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"Multiple acute studies + 1 chronic study","evidence":"Acute GH release after hexarelin is large and well established. Over 16 weeks of twice-daily dosing the response attenuated and then recovered after stopping — a tolerance effect typical of the class.","references":[{"citation":"Rahim A, et al. Growth hormone status during long-term hexarelin therapy.","where":"J Clin Endocrinol Metab, 1998;83:1644–1649","url":"https://pubmed.ncbi.nlm.nih.gov/9589671/"}],"verbatim":{"text":"chronic hexarelin therapy results in a partial and reversible attenuation of the GH response to hexarelin.","citation":"Rahim A, et al. Growth hormone status during long-term hexarelin therapy.","url":"https://pubmed.ncbi.nlm.nih.gov/9589671/"}},{"outcome":"Body composition","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 chronic study (n small)","evidence":"In the only sustained-dosing study, IGF-1, body fat, lean mass and bone density did not change significantly over 16 weeks.","references":[{"citation":"Rahim A, et al. Growth hormone status during long-term hexarelin therapy.","where":"J Clin Endocrinol Metab, 1998;83:1644–1649","url":"https://pubmed.ncbi.nlm.nih.gov/9589671/"}],"verbatim":{"text":"In the present study, the biological impact of this hexarelin schedule on the GH-IGF-I axis seems to be minimal.","citation":"Rahim A, et al. Growth hormone status during long-term hexarelin therapy.","url":"https://pubmed.ncbi.nlm.nih.gov/9589671/"}},{"outcome":"Cardiac effects","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Mechanistic only","evidence":"Hexarelin binds a receptor (CD36) in the heart and has cardiovascular effects in animals and acute human physiology studies. No controlled trial has tested a clinical cardiac outcome.","references":[{"citation":"Arvat E, et al. Endocrine activities of ghrelin in humans: comparison with hexarelin and GHRH.","where":"J Clin Endocrinol Metab, 2001;86:1169–1174","url":"https://pubmed.ncbi.nlm.nih.gov/11238504/"}]},{"outcome":"Safety in humans","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":true,"human_studies":"Early-phase","evidence":"Short-term dosing is generally well tolerated in the small studies; transient flushing and mild cortisol/prolactin rises are described. No long-term safety data.","references":[{"citation":"Rahim A, et al. Growth hormone status during long-term hexarelin therapy.","where":"J Clin Endocrinol Metab, 1998;83:1644–1649","url":"https://pubmed.ncbi.nlm.nih.gov/9589671/"}]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; a 'research use only' label does not change that."},{"region":"United States","status":"Not approved","note":"Not an approved drug and not a dietary-supplement ingredient. Sold as a 'research chemical' outside the medical system; the FDA has warned against several compounds in this class."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it for human use is an offence under the Human Medicines Regulations 2012."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG. Supply without a prescription is unlawful; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it for human use is illegal."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"WADA class S2.2: growth-hormone secretagogues and GH-releasing peptides are banned in and out of competition."}],"faq":[{"q":"Does hexarelin build muscle?","a":"There is no controlled human evidence that it changes muscle or body composition. The one sustained-dosing study found no significant change in lean mass, fat or IGF-1 over 16 weeks."},{"q":"Why does it 'stop working'?","a":"Like other GH-releasing peptides, continued use desensitises the receptor, so the growth-hormone response fades over weeks. It recovered after stopping in the one study that measured it."},{"q":"Is it allowed in sport?","a":"No. GH-releasing peptides are prohibited at all times under WADA category S2."}],"references":[{"cite":"Rahim A, et al. Growth hormone status during long-term hexarelin therapy.","where":"J Clin Endocrinol Metab, 1998;83:1644–1649","url":"https://pubmed.ncbi.nlm.nih.gov/9589671/","note":"16 weeks; GH response attenuates, IGF-1 and body composition unchanged."},{"cite":"Arvat E, et al. Endocrine activities of ghrelin in humans: comparison with hexarelin and GHRH.","where":"J Clin Endocrinol Metab, 2001;86:1169–1174","url":"https://pubmed.ncbi.nlm.nih.gov/11238504/","note":"Acute GH-releasing potency of hexarelin in people."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Grade C on a real but self-limiting GH effect and no outcome data."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"ghrp-2","name":"GHRP-2","aliases":["pralmorelin","KP-102","GH-releasing peptide-2"],"url":"https://lyoresearch.com/compounds/ghrp-2","class":{"id":"gh-secretagogues","name":"GH secretagogues (GHRPs)","url":"https://lyoresearch.com/classes/gh-secretagogues"},"summary":"GHRP-2, or pralmorelin, is a synthetic six-amino-acid growth-hormone-releasing peptide. It reliably and measurably raises growth hormone, and on that basis is approved in Japan as a diagnostic test for growth-hormone deficiency. Like natural ghrelin it also increases appetite in short human studies. What it does not have is any trial showing it builds muscle, burns fat or improves body composition — the uses it is actually sold for. It is banned in sport.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Diagnostic-grade + small studies","regulatory_status":"Approved (diagnostic, Japan)","molecule":{"formula":"C45H55N9O6","molecular_weight":"818.0","cas":"158861-67-7","pubchem_cid":6918245,"note":null},"pharmacokinetics":{"basis":"human","route":"Intravenous (diagnostic use in Japan as pralmorelin)","half_life":"Human intravenous use is documented; no primary half-life figure was found","licensed_regimen":null,"product":null,"source":{"title":"Pralmorelin. Drugs R D 2004;5:236–239","url":"https://pubmed.ncbi.nlm.nih.gov/15230633/"}},"outcomes":[{"outcome":"Growth hormone release (diagnostic)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Approval-grade diagnostic studies","evidence":"GHRP-2 produces a large, reproducible GH rise that cleanly separates GH-deficient from healthy people — the basis of its Japanese approval as a diagnostic agent.","references":[{"citation":"Chihara K, et al. A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency.","where":"Eur J Endocrinol, 2007;157:19–27","url":"https://pubmed.ncbi.nlm.nih.gov/17609397/"}],"verbatim":{"text":"Peak GH concentrations after GHRP-2 were significantly (P<0.001) lower in patients (1.36+/-2.60 microg/l) than the healthy group (84.6+/-60.9 microg/l) with no difference between hypothalamic and pituitary diseases.","citation":"Chihara K, et al. A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency.","url":"https://pubmed.ncbi.nlm.nih.gov/17609397/"}},{"outcome":"Appetite","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"Small crossover study (n=7)","evidence":"As a ghrelin mimic, GHRP-2 increased food intake in healthy men in a controlled infusion study — a real acute effect, studied in very few people.","references":[{"citation":"Laferrère B, et al. Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.","where":"J Clin Endocrinol Metab, 2005;90:611–614","url":"https://pubmed.ncbi.nlm.nih.gov/15699539/"}],"verbatim":{"text":"Similar to what has been reported for ghrelin administration, our subjects ate 35.9 +/- 10.9% more when infused with GHRP-2 vs. saline, with every subject increasing their intake even when calculated per kg body weight (136.0 +/- 13.0 kJ/kg [32.5 +/- 3.1 kcal/kg] vs. 101.3 +/- 10.5 kJ/kg [24.2 +/- 2.5 kcal/kg], p = 0.008).","citation":"Laferrère B, et al. Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.","url":"https://pubmed.ncbi.nlm.nih.gov/15699539/"}},{"outcome":"Body composition","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"No controlled trial has tested whether repeated GHRP-2 changes muscle or fat in humans. The physique claims are extrapolation from the acute GH rise.","references":[{"citation":"Chihara K, et al. A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency.","where":"Eur J Endocrinol, 2007;157:19–27","url":"https://pubmed.ncbi.nlm.nih.gov/17609397/"}]},{"outcome":"Safety in humans","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":true,"human_studies":"Diagnostic use","evidence":"As a single diagnostic dose it is well tolerated, with flushing the main effect. Safety of repeated self-dosing is not established, and it raises cortisol and prolactin more than the most selective secretagogues.","references":[{"citation":"Chihara K, et al. A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency.","where":"Eur J Endocrinol, 2007;157:19–27","url":"https://pubmed.ncbi.nlm.nih.gov/17609397/"}]}],"regions":[{"region":"European Union","status":"Not authorised","note":"No EMA authorisation. Supplying it for human use is an offence under national medicines law."},{"region":"United States","status":"Not approved","note":"Not an FDA-approved drug; sold as a research chemical. The FDA has flagged GHRPs among peptides that should not be in compounded products."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence; supply for human use is an offence."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG; imports without a prescription are seized."},{"region":"Japan","status":"Approved (diagnostic)","note":"Pralmorelin (GHRP Kaken) is approved as a diagnostic agent for growth-hormone secretion — not as a treatment."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"WADA class S2.2: GH-releasing peptides are banned in and out of competition."}],"faq":[{"q":"Is GHRP-2 approved?","a":"Only in Japan, and only as a diagnostic test (pralmorelin) for growth-hormone deficiency — a single injection to measure pituitary function. It is not approved anywhere as a treatment for muscle, fat or ageing."},{"q":"Does it build muscle?","a":"No trial has tested that. It reliably raises growth hormone acutely, but no controlled study has shown that repeated use changes body composition."},{"q":"Why does it make you hungry?","a":"It mimics ghrelin, the hunger hormone, at the same receptor — so it drives appetite as well as growth-hormone release."}],"references":[{"cite":"Chihara K, et al. A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency.","where":"Eur J Endocrinol, 2007;157:19–27","url":"https://pubmed.ncbi.nlm.nih.gov/17609397/","note":"77 healthy + 58 GH-deficient adults; the diagnostic basis."},{"cite":"Laferrère B, et al. Growth hormone releasing peptide-2 (GHRP-2), like ghrelin, increases food intake in healthy men.","where":"J Clin Endocrinol Metab, 2005;90:611–614","url":"https://pubmed.ncbi.nlm.nih.gov/15699539/","note":"7 lean men; the appetite data."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Grade A for the diagnostic GH response, D for the marketed physique use."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"ghrp-6","name":"GHRP-6","aliases":["GH-releasing peptide-6","His-D-Trp-Ala-Trp-D-Phe-Lys"],"url":"https://lyoresearch.com/compounds/ghrp-6","class":{"id":"gh-secretagogues","name":"GH secretagogues (GHRPs)","url":"https://lyoresearch.com/classes/gh-secretagogues"},"summary":"GHRP-6 is the first of the growth-hormone-releasing peptides, a synthetic six-amino-acid ghrelin mimic. In studies it raises growth hormone as reliably as the standard insulin tolerance test, which makes it a useful diagnostic; it also stimulates appetite. As with the rest of its class, there is no controlled human trial showing it builds muscle or reduces fat, and it is banned in sport.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Diagnostic studies + small work","regulatory_status":"Not approved","molecule":{"formula":"C46H56N12O6","molecular_weight":"873.0","cas":null,"pubchem_cid":4345065,"note":null},"pharmacokinetics":{"basis":"human","route":"Intravenous bolus (9 healthy men)","half_life":"About 2.5 hours elimination half-life; distribution half-life about 8 minutes","licensed_regimen":null,"product":null,"source":{"title":"Cabrales A, et al. Pharmacokinetic study of growth hormone-releasing peptide 6 (GHRP-6) in nine male healthy volunteers. Eur J Pharm Sci 2013;48:40–46","url":"https://pubmed.ncbi.nlm.nih.gov/23099431/"}},"outcomes":[{"outcome":"Growth hormone release (diagnostic)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"Diagnostic comparison studies","evidence":"GHRP-6, alone or with GHRH, stimulated growth hormone as sensitively and specifically as the insulin tolerance test for diagnosing adult GH deficiency.","references":[{"citation":"Petersenn S, et al. Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or with GHRH: comparison with the insulin tolerance test.","where":"Eur J Endocrinol, 2002;146:667–672","url":"https://pubmed.ncbi.nlm.nih.gov/11980622/"}],"verbatim":{"text":"The results suggest that testing with GHRP-6 or GHRP-6+GHRH is as sensitive and specific as an ITT for the diagnosis of adult GH deficiency.","citation":"Petersenn S, et al. Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or with GHRH: comparison with the insulin tolerance test.","url":"https://pubmed.ncbi.nlm.nih.gov/11980622/"}},{"outcome":"Appetite","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Small human studies","evidence":"As a ghrelin-receptor agonist it increases hunger; the human appetite data are smaller and less quantified than for GHRP-2.","references":[{"citation":"Petersenn S, et al. Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or with GHRH: comparison with the insulin tolerance test.","where":"Eur J Endocrinol, 2002;146:667–672","url":"https://pubmed.ncbi.nlm.nih.gov/11980622/"}]},{"outcome":"Body composition","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"No controlled trial has tested whether repeated GHRP-6 changes muscle or fat in people.","references":[{"citation":"Petersenn S, et al. Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or with GHRH: comparison with the insulin tolerance test.","where":"Eur J Endocrinol, 2002;146:667–672","url":"https://pubmed.ncbi.nlm.nih.gov/11980622/"}]},{"outcome":"Safety in humans","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":true,"human_studies":"Diagnostic use","evidence":"As a single diagnostic dose, flushing was the only side effect reported. Repeated-use safety is not established.","references":[{"citation":"Petersenn S, et al. Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or with GHRH: comparison with the insulin tolerance test.","where":"Eur J Endocrinol, 2002;146:667–672","url":"https://pubmed.ncbi.nlm.nih.gov/11980622/"}],"verbatim":{"text":"During administration of GHRP-6, the only side effects observed were flush symptoms.","citation":"Petersenn S, et al. Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or with GHRH: comparison with the insulin tolerance test.","url":"https://pubmed.ncbi.nlm.nih.gov/11980622/"}}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; a 'research use only' label does not change that."},{"region":"United States","status":"Not approved","note":"Not an approved drug and not a dietary-supplement ingredient. Sold as a 'research chemical' outside the medical system; the FDA has warned against several compounds in this class."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it for human use is an offence under the Human Medicines Regulations 2012."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG. Supply without a prescription is unlawful; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it for human use is illegal."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"WADA class S2.2: growth-hormone secretagogues and GH-releasing peptides are banned in and out of competition."}],"faq":[{"q":"What is GHRP-6 actually good for?","a":"As a diagnostic stimulus for growth-hormone deficiency it performs as well as the standard insulin tolerance test. That is its only evidence-backed use."},{"q":"Does it build muscle?","a":"No controlled human trial has tested it. Like the rest of the class, it raises growth hormone acutely but has no outcome data for body composition."},{"q":"How is it different from GHRP-2?","a":"They are close cousins. GHRP-2 has a formal diagnostic approval in Japan and better-quantified appetite data; GHRP-6 is the older molecule and drives hunger somewhat more prominently."}],"references":[{"cite":"Petersenn S, et al. Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or with GHRH: comparison with the insulin tolerance test.","where":"Eur J Endocrinol, 2002;146:667–672","url":"https://pubmed.ncbi.nlm.nih.gov/11980622/","note":"20 patients; diagnostic performance equal to the ITT."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Grade reflects diagnostic-grade GH data and no outcome trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"nad-plus","name":"NAD+ and precursors","aliases":["NAD+","NMN","nicotinamide mononucleotide","NR","nicotinamide riboside","NAD injection"],"url":"https://lyoresearch.com/compounds/nad-plus","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"NAD+ is a coenzyme every cell uses for energy metabolism; it is not a peptide, but its precursors (NMN and NR) and intravenous NAD+ itself are sold across the same anti-ageing market. Randomised trials show the oral precursors reliably raise NAD+ levels and are well tolerated. What they have not yet shown is a clear clinical benefit — trials of metabolism, muscle and ageing are small, mixed and contested. Intravenous NAD+ has essentially no controlled evidence.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Several RCTs of precursors","regulatory_status":"Sold as supplement (NR/NMN); IV NAD+ unlicensed","molecule":{"formula":"C21H27N7O14P2","molecular_weight":"663.4","cas":"53-84-9","pubchem_cid":5892,"note":"Recorded as nadide, the oxidised coenzyme"},"pharmacokinetics":{"basis":"human","route":"Intravenous infusion (healthy men, 750 mg over 6 hours)","half_life":"No half-life reported; plasma NAD+ did not rise for the first 2 hours of infusion, then rose about four-fold by 6 hours","licensed_regimen":null,"product":null,"source":{"title":"Grant R, et al. A pilot study investigating changes in the human plasma and urine NAD+ metabolome during a 6 hour intravenous infusion of NAD+. Front Aging Neurosci 2019;11:257","url":"https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2019.00257/full"}},"outcomes":[{"outcome":"Raising NAD+ levels","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"Multiple RCTs (NR, NMN)","evidence":"Oral nicotinamide riboside and NMN reliably and safely increase blood NAD+ in randomised trials — the one thing that is well established.","references":[{"citation":"Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.","where":"Nat Commun, 2018;9:1286","url":"https://pubmed.ncbi.nlm.nih.gov/29599478/"}],"verbatim":{"text":"chronic supplementation with the NAD+ precursor vitamin, nicotinamide riboside (NR), is well tolerated and effectively stimulates NAD+ metabolism in healthy middle-aged and older adults.","citation":"Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.","url":"https://pubmed.ncbi.nlm.nih.gov/29599478/"}},{"outcome":"Insulin sensitivity / metabolic health","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 small RCT (n=25), contested","evidence":"A 10-week NMN trial in prediabetic postmenopausal women improved muscle insulin sensitivity — a single small study whose interpretation was publicly disputed and which has not been replicated.","references":[{"citation":"Yoshino M, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.","where":"Science, 2021;372:1224–1229","url":"https://pubmed.ncbi.nlm.nih.gov/33888596/"}],"verbatim":{"text":"These results demonstrate that NMN increases muscle insulin sensitivity, insulin signaling, and remodeling in women with prediabetes who are overweight or obese.","citation":"Yoshino M, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.","url":"https://pubmed.ncbi.nlm.nih.gov/33888596/"}},{"outcome":"Anti-ageing / physical function","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"No outcome trials","evidence":"Despite the marketing, no trial has shown NAD+ or its precursors slow ageing or improve hard clinical outcomes in people. Some trials found no effect on muscle mitochondrial function.","references":[{"citation":"Dollerup OL, et al. Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men.","where":"J Physiol, 2020;598:731–754","url":"https://pubmed.ncbi.nlm.nih.gov/31710095/"}]},{"outcome":"Safety (oral precursors)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"Multiple RCTs","evidence":"Oral NR and NMN are well tolerated in trials up to several months. Intravenous NAD+ is a different matter — unstudied in controlled trials and associated with infusion reactions.","references":[{"citation":"Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.","where":"Nat Commun, 2018;9:1286","url":"https://pubmed.ncbi.nlm.nih.gov/29599478/"}]}],"regions":[{"region":"European Union","status":"Mixed; NMN restricted","note":"NR is an authorised novel food; NMN's food status is unsettled in the EU. Intravenous NAD+ for 'wellness' is an unlicensed medical use."},{"region":"United States","status":"Supplement status contested","note":"NR is sold as a dietary supplement. The FDA has taken the position that NMN is excluded from the supplement definition because it was investigated as a drug; enforcement is unsettled. IV NAD+ is offered by clinics without FDA approval."},{"region":"United Kingdom","status":"Supplement / unlicensed","note":"Oral precursors are sold as supplements; IV NAD+ is an unlicensed medical service."},{"region":"Australia","status":"Supplement / clinic use","note":"Oral products sold as complementary medicines; IV NAD+ offered by some clinics outside standard registration."},{"region":"Canada","status":"Natural health product / clinic use","note":"Some oral products carry NPN numbers; IV NAD+ is a clinic service, not an approved therapy."},{"region":"Sport (WADA)","status":"Not prohibited","note":"NAD+ and its precursors are not on the 2026 Prohibited List."}],"faq":[{"q":"Do NAD+ supplements work?","a":"They reliably raise NAD+ levels and are well tolerated. Whether that produces any health benefit is unproven — the outcome trials so far are small, mixed and, in the most-cited case, contested."},{"q":"Is NMN or NR better?","a":"No head-to-head trial answers that. Both raise NAD+; neither has shown a clear clinical benefit in a large trial."},{"q":"What about NAD+ IV drips?","a":"Intravenous NAD+ has essentially no controlled-trial evidence. The randomised data are for the oral precursors, not the drips."}],"references":[{"cite":"Martens CR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults.","where":"Nat Commun, 2018;9:1286","url":"https://pubmed.ncbi.nlm.nih.gov/29599478/","note":"24 adults, crossover; NR raises NAD+, well tolerated."},{"cite":"Yoshino M, et al. Nicotinamide mononucleotide increases muscle insulin sensitivity in prediabetic women.","where":"Science, 2021;372:1224–1229","url":"https://pubmed.ncbi.nlm.nih.gov/33888596/","note":"25 women, 10 weeks; single, contested trial."},{"cite":"Dollerup OL, et al. Nicotinamide riboside does not alter mitochondrial respiration, content or morphology in skeletal muscle from obese and insulin-resistant men.","where":"J Physiol, 2020;598:731–754","url":"https://pubmed.ncbi.nlm.nih.gov/31710095/","note":"A representative null metabolic result."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Grade B for raising NAD+, C/D for clinical outcomes."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"kpv","name":"KPV","aliases":["Lys-Pro-Val","α-MSH(11-13)","melanocortin tripeptide"],"url":"https://lyoresearch.com/compounds/kpv","class":{"id":"healing-peptides","name":"Tissue-repair peptides","url":"https://lyoresearch.com/classes/healing-peptides"},"summary":"KPV is a three-amino-acid fragment (lysine-proline-valine) from the tail of the hormone α-MSH, studied for anti-inflammatory effects. In cell and mouse models of gut inflammation it dampens inflammatory signalling, which is the basis of its reputation for 'healing' and gut health. No controlled human trial of any kind has tested it. It is not approved anywhere.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 controlled","regulatory_status":"Not approved","molecule":{"formula":"C16H30N4O4","molecular_weight":"342.43","cas":"67727-97-3","pubchem_cid":125672,"note":"Recorded as MSH(11-13)"},"pharmacokinetics":{"basis":"none","route":"Oral or injected as sold; no human study","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Intestinal / systemic inflammation","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"KPV reduces inflammation in mouse models of colitis and in cultured immune and epithelial cells, including when delivered by targeted nanoparticles. No human trial has tested it.","references":[]},{"outcome":"Wound healing / recovery","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Popular claims about wound healing and recovery extend from the α-MSH anti-inflammatory literature; there is no controlled human study of KPV for these uses.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None","evidence":"No human dosing study exists, so there is no safety dataset at any dose or route.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; a 'research use only' label does not change that."},{"region":"United States","status":"Not approved","note":"Not an approved drug and not a dietary-supplement ingredient. Sold as a 'research chemical' outside the medical system; the FDA has warned against several compounds in this class."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it for human use is an offence under the Human Medicines Regulations 2012."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG. Supply without a prescription is unlawful; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it for human use is illegal."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"As a non-approved substance, KPV falls under WADA class S0 (non-approved substances) and is prohibited in and out of competition."}],"faq":[{"q":"Does KPV help gut inflammation in people?","a":"Unknown. The anti-inflammatory data are from mouse colitis models and cell studies. It has never been tested in a controlled human trial."},{"q":"Is KPV related to Melanotan?","a":"It is the small anti-inflammatory tail of the same parent hormone (α-MSH), but without the tanning and appetite effects. Different fragment, different activity."}],"references":[{"cite":"Kannengiesser K, et al. Melanocortin-derived tripeptide KPV has anti-inflammatory potential in murine models of inflammatory bowel disease.","where":"Inflamm Bowel Dis, 2008;14:324–331","url":"https://pubmed.ncbi.nlm.nih.gov/18092346/","note":"Mouse colitis models."},{"cite":"Xiao B, et al. Orally targeted delivery of tripeptide KPV via hyaluronic-acid-functionalized nanoparticles alleviates ulcerative colitis.","where":"Mol Ther, 2017;25:1628–1640","url":"https://pubmed.ncbi.nlm.nih.gov/28143741/","note":"Mouse targeted-delivery study."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. All outcomes graded D on absence of human trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"humanin","name":"Humanin","aliases":["HN","HNG (humanin analogue)","mitochondrial-derived peptide"],"url":"https://lyoresearch.com/compounds/humanin","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"Humanin is a small peptide encoded within mitochondrial DNA, discovered in 2001, with cell-protective effects in laboratory models of Alzheimer's, diabetes and cardiovascular stress. In people, blood levels of humanin fall with age and vary with disease — but that is observation of the humanin people already have, not a test of giving more. No controlled human trial has administered it. It is not approved anywhere.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 controlled","regulatory_status":"Not approved","molecule":{"formula":"C119H204N34O32S2","molecular_weight":"2687.2","cas":"330936-69-1","pubchem_cid":16131438,"note":null},"pharmacokinetics":{"basis":"none","route":"Injected as sold; no human administration study","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Cytoprotection / metabolic health","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Humanin protects neurons and other cells from stress in laboratory and animal models. Human work is observational — levels correlate with age and disease — and cannot show what supplementation would do.","references":[]},{"outcome":"Ageing / longevity","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Association only","evidence":"Higher circulating humanin has been associated with markers of health and with dietary patterns in cohort studies. Association in people who already have it is not an intervention result.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None","evidence":"No human dosing study of any kind, and therefore no safety data.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; a 'research use only' label does not change that."},{"region":"United States","status":"Not approved","note":"Not an approved drug and not a dietary-supplement ingredient. Sold as a 'research chemical' outside the medical system; the FDA has warned against several compounds in this class."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it for human use is an offence under the Human Medicines Regulations 2012."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG. Supply without a prescription is unlawful; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it for human use is illegal."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"As a non-approved substance, humanin falls under WADA class S0 (non-approved substances) and is prohibited in and out of competition."}],"faq":[{"q":"Does humanin slow ageing?","a":"Unknown. The protective effects are from cell and animal studies. Human research so far measures naturally occurring humanin; it has never been given to people in a controlled trial."},{"q":"Is it the same idea as MOTS-c?","a":"Yes — both are peptides encoded in mitochondrial DNA, with interesting lab biology and no human intervention trials."}],"references":[{"cite":"Hashimoto Y, et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer's disease genes and Aβ (humanin).","where":"Proc Natl Acad Sci USA, 2001;98:6336–6341","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Hashimoto+humanin+rescue+factor+Alzheimer+2001+PNAS","note":"The discovery paper."},{"cite":"Observational human studies of circulating humanin with age, disease and diet.","where":"Various, e.g. Aging (Albany NY) and Front Nutr, 2018–2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=humanin+mitochondrial+derived+peptide+humans+plasma+aging","note":"Association studies; not interventions."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. All outcomes graded D on absence of human intervention trials."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"dihexa","name":"Dihexa","aliases":["PNB-0408","N-hexanoic-Tyr-Ile-(6) aminohexanoic amide","angiotensin IV analogue"],"url":"https://lyoresearch.com/compounds/dihexa","class":{"id":"nootropic-peptides","name":"Nootropic and sleep peptides","url":"https://lyoresearch.com/classes/nootropic-peptides"},"summary":"Dihexa is a small synthetic molecule derived from angiotensin IV, studied for its striking ability to promote new synapse formation in rodents and its potential in memory and Parkinson's models. It is not a true peptide and, more importantly, has never been tested in a controlled human trial. It is sold as a 'nootropic' research chemical with no human evidence and no safety data.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 controlled","regulatory_status":"Not approved","molecule":{"formula":"C27H44N4O5","molecular_weight":"504.7","cas":"1401708-83-5","pubchem_cid":129010512,"note":null},"pharmacokinetics":{"basis":"none","route":"Oral or topical as sold; no human study","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Cognition / synapse formation","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Dihexa promotes synaptogenesis and improves memory in rodent models, including models of Alzheimer's and Parkinson's disease. No human trial has tested it.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None","evidence":"No human dosing study exists. A molecule that drives new synapse formation this potently has an obvious theoretical concern — uncontrolled growth signalling — that has never been evaluated in people.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; a 'research use only' label does not change that."},{"region":"United States","status":"Not approved","note":"Not an approved drug and not a dietary-supplement ingredient. Sold as a 'research chemical' outside the medical system; the FDA has warned against several compounds in this class."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it for human use is an offence under the Human Medicines Regulations 2012."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG. Supply without a prescription is unlawful; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it for human use is illegal."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"As a non-approved substance, dihexa falls under WADA class S0 (non-approved substances) and is prohibited in and out of competition."}],"faq":[{"q":"Does dihexa improve memory in people?","a":"Unknown. The memory and synapse data are entirely from rodents. There is no controlled human trial."},{"q":"Is dihexa safe?","a":"There is no human safety data at all. Its mechanism — potently driving new synapse and growth signalling — is a theoretical concern that has never been evaluated in people."}],"references":[{"cite":"McCoy AT, et al. Evaluation of metabolically stabilized angiotensin IV analogs as pro-cognitive/anti-dementia agents (dihexa).","where":"J Pharmacol Exp Ther, 2013;344:141–154","url":"https://pubmed.ncbi.nlm.nih.gov/?term=McCoy+dihexa+angiotensin+IV+cognitive+2013","note":"The rodent synaptogenesis work."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Grade D on absence of any human trial."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"5-amino-1mq","name":"5-Amino-1MQ","aliases":["5-amino-1-methylquinolinium","NNMT inhibitor"],"url":"https://lyoresearch.com/compounds/5-amino-1mq","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"5-Amino-1MQ is a small molecule — not a peptide — that blocks an enzyme called NNMT, which is elevated in the fat tissue of obese people. In mice, inhibiting NNMT reduces fat mass and improves metabolic markers, which is the basis of its sale as a weight-loss and metabolic 'peptide'. It has never been tested in a controlled human trial and is not approved anywhere.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 controlled","regulatory_status":"Not approved","molecule":{"formula":"C10H11N2+","molecular_weight":"159.21","cas":"685079-15-6","pubchem_cid":950107,"note":null},"pharmacokinetics":{"basis":"animal","route":"Oral as sold; no human study","half_life":"No human pharmacokinetic data; a rat PK assay paper exists","licensed_regimen":null,"product":null,"source":{"title":"Development and validation of an LC–MS/MS assay for 5-amino-1-methylquinolinium in rat plasma: application to pharmacokinetic and oral bioavailability studies. J Pharm Biomed Anal 2021","url":"https://www.sciencedirect.com/science/article/abs/pii/S0731708521003666"}},"outcomes":[{"outcome":"Fat loss / metabolic health","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"Inhibiting NNMT with 5-amino-1MQ reduced fat mass and improved metabolic measures in mouse models of diet-induced obesity. No human trial has tested it for weight or metabolism.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None","evidence":"No human dosing study exists; there is no safety dataset. NNMT sits at a hub of NAD+ and methylation metabolism, so systemic inhibition has plausible but unstudied off-target effects.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law; a 'research use only' label does not change that."},{"region":"United States","status":"Not approved","note":"Not an approved drug and not a dietary-supplement ingredient. Sold as a 'research chemical' outside the medical system; the FDA has warned against several compounds in this class."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"Not licensed by the MHRA. Selling or supplying it for human use is an offence under the Human Medicines Regulations 2012."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG. Supply without a prescription is unlawful; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number; selling it for human use is illegal."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"As a non-approved substance, 5-amino-1MQ falls under WADA class S0 (non-approved substances) and is prohibited in and out of competition."}],"faq":[{"q":"Does 5-amino-1MQ cause weight loss in people?","a":"Unknown. The fat-loss data are from mice. There is no controlled human trial of the compound for weight or metabolism."},{"q":"Is it a peptide?","a":"No. It is a small synthetic molecule that inhibits the NNMT enzyme. It is grouped with peptides only because it is marketed and injected alongside them."}],"references":[{"cite":"Neelakantan H, et al. Selective and membrane-permeable small-molecule inhibitors of NNMT reduce adiposity in diet-induced obese mice (5-amino-1MQ).","where":"Biochem Pharmacol, 2018;147:141–152","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Neelakantan+NNMT+inhibitor+5-amino-1MQ+adiposity+mice","note":"The mouse fat-loss work."},{"cite":"Yang M, et al. NNMT in cancer-associated fibroblasts drives tumour progression; inhibition with 5-amino-1-methylquinolinium.","where":"J Immunother Cancer, 2024;12:e008340","url":"https://pubmed.ncbi.nlm.nih.gov/39067875/","note":"Illustrates the enzyme's broader biology; not a metabolic trial."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Grade D on absence of any human trial."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"orforglipron","name":"Orforglipron","aliases":["Foundayo","LY3502970","oral GLP-1","small-molecule GLP-1 receptor agonist"],"url":"https://lyoresearch.com/compounds/orforglipron","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Orforglipron (Foundayo) is a once-daily tablet that activates the GLP-1 receptor. It is not a peptide — it is a small molecule, which is why it survives digestion and needs no injection, refrigeration or food restriction. Its phase 3 programme is published: about 11% average weight loss over 72 weeks in obesity, and HbA1c reductions of roughly 1.5 points in early type 2 diabetes. The FDA approved it for weight management on 1 April 2026. The effect is smaller than injected tirzepatide or semaglutide; the delivery is far easier.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"Phase 3 programme published","regulatory_status":"Approved (Rx) — United States","molecule":{"formula":"C48H48F2N10O5","molecular_weight":"883.0","cas":"2212020-52-3","pubchem_cid":137319706,"note":null},"pharmacokinetics":{"basis":"label","route":"Oral tablet, once daily","half_life":"About 29-49 hours","licensed_regimen":"0.8 mg daily, then after ≥30 days 2.5 mg, then 5.5 mg, then 9, 14.5 or 17.2 mg daily with ≥30 days between escalations; maximum 17.2 mg daily","product":"Foundayo","source":{"title":"Foundayo prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8ac446c5-feba-474f-a103-23facb9b5c62"}},"outcomes":[{"outcome":"Body weight","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Phase 3 RCT (n=3,127) + programme","evidence":"ATTAIN-1, 72 weeks in adults with obesity and no diabetes: −11.2% on the 36 mg dose versus −2.1% on placebo. 36.0% lost at least 15% of body weight, against 5.9% on placebo.","references":[{"citation":"Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1).","where":"N Engl J Med, 2025;393:1796–1806","url":"https://pubmed.ncbi.nlm.nih.gov/40960239/"}],"verbatim":{"text":"The mean change in body weight from baseline to week 72 was -7.5% (95% confidence interval [CI], -8.2 to -6.8) with 6 mg of orforglipron, -8.4% (95% CI, -9.1 to -7.7) with 12 mg of orforglipron, and -11.2% (95% CI, -12.0 to -10.4) with 36 mg of orforglipron, as compared with -2.1% (95% CI, -2.8 to -1.4) with placebo (P<0.001 for all comparisons with placebo).","citation":"Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1).","url":"https://pubmed.ncbi.nlm.nih.gov/40960239/"}},{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Phase 3 RCT (n=559) + programme","evidence":"ACHIEVE-1, 40 weeks in type 2 diabetes managed by diet and exercise alone: HbA1c fell 1.24–1.48 points versus 0.41 on placebo, bringing the average to 6.5–6.7%.","references":[{"citation":"Rosenstock J, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes (ACHIEVE-1).","where":"N Engl J Med, 2025;393:1065–1076","url":"https://pubmed.ncbi.nlm.nih.gov/40544435/"}],"verbatim":{"text":"At week 40, the estimated mean change from baseline in the glycated hemoglobin level was -1.24 percentage points with the 3-mg dose, -1.47 percentage points with the 12-mg dose, -1.48 percentage points with the 36-mg dose, and -0.41 percentage points with placebo.","citation":"Rosenstock J, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes (ACHIEVE-1).","url":"https://pubmed.ncbi.nlm.nih.gov/40544435/"}},{"outcome":"Major cardiovascular events","grade":"B","grade_meaning":"probable, not settled","effect_size":"not measurable","adverse":false,"human_studies":"1 phase 3 safety RCT (ACHIEVE-4, n=2,749, median 2 yr)","evidence":"ACHIEVE-4, published in The Lancet on 30 September 2026: adults with type 2 diabetes, overweight or obesity and established cardiovascular or chronic kidney disease took orforglipron or insulin glargine, open label. A major cardiovascular event occurred in 4.2% on orforglipron and 5.0% on glargine (hazard ratio 0.84, 95% CI 0.59–1.20). That meets non-inferiority, so cardiovascular safety is confirmed; the interval crosses 1, so a reduction in events is not shown. Deaths were 1.4% against 3.2%, in a trial built to test safety, not that difference. Clinically significant hypoglycaemia: 6.8% vs 19.2%.","references":[{"citation":"Klein KR, et al. Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.","where":"Lancet, 2026 (online 30 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42815506/"}],"verbatim":{"text":"Over a median follow-up of 2 years, the primary outcome occurred in 57 (4·2%) of 1358 orforglipron participants and 67 (5·0%) of 1343 insulin glargine participants, showing non-inferiority to insulin glargine for MACE-4 (HR 0·84; 95% CI 0·59-1·20; p<0·0001 for non-inferiority).","citation":"Klein KR, et al. Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.","url":"https://pubmed.ncbi.nlm.nih.gov/42815506/"}},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"Phase 3 programme","evidence":"The familiar incretin profile. In ATTAIN-1, adverse events caused 5.3–10.3% of participants to stop, against 2.7% on placebo. In ACHIEVE-4, gastrointestinal events were reported in 62.1% on orforglipron against 14.2% on insulin glargine.","references":[{"citation":"Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1).","where":"N Engl J Med, 2025;393:1796–1806","url":"https://pubmed.ncbi.nlm.nih.gov/40960239/"},{"citation":"Klein KR, et al. Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.","where":"Lancet, 2026 (online 30 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42815506/"}],"verbatim":{"text":"The most common adverse events with orforglipron were gastrointestinal effects, which were mostly mild to moderate.","citation":"Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1).","url":"https://pubmed.ncbi.nlm.nih.gov/40960239/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"No EMA marketing authorisation. Under regulatory review following the phase 3 programme."},{"region":"United States","status":"Approved, prescription-only","note":"Foundayo approved by the FDA on 1 April 2026 to reduce excess body weight and maintain weight reduction in adults with obesity, or with overweight and at least one weight-related condition. Anything sold as orforglipron without a prescription is not the licensed product."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Not prohibited","note":"GLP-1 receptor agonists are not on the 2026 Prohibited List."}],"faq":[{"q":"Is orforglipron as good as Ozempic or Mounjaro?","a":"For weight, no. About 11% average loss at 72 weeks compares with roughly 15% for semaglutide and 21% for tirzepatide in their own trials. Cross-trial comparison is unreliable, but the gap is consistent. The trade is that it is a daily tablet with no injection and no food timing."},{"q":"Is orforglipron a peptide?","a":"No. It is a small synthetic molecule that happens to hit the same receptor. That is precisely why it works as a pill."},{"q":"Can I buy it?","a":"In the United States it is a prescription medicine: the FDA approved it as Foundayo on 1 April 2026 for weight management. LYO has not verified an approval in the other regions on this page. Products sold under the name without a prescription are not the licensed drug."}],"references":[{"cite":"Wharton S, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist for obesity treatment (ATTAIN-1).","where":"N Engl J Med, 2025;393:1796–1806","url":"https://pubmed.ncbi.nlm.nih.gov/40960239/","note":"3,127 adults, 72 weeks."},{"cite":"Rosenstock J, et al. Orforglipron, an oral small-molecule GLP-1 receptor agonist, in early type 2 diabetes (ACHIEVE-1).","where":"N Engl J Med, 2025;393:1065–1076","url":"https://pubmed.ncbi.nlm.nih.gov/40544435/","note":"559 participants, 40 weeks."},{"cite":"Horn DB, et al. Orforglipron for obesity in people with type 2 diabetes (ATTAIN-2): a phase 3 randomised trial.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/41275875/"},{"cite":"Wharton S, et al. Hepatic safety of orforglipron: a pooled analysis of the phase 3 clinical trials.","where":"Diabetes Obes Metab, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42338042/"},{"cite":"Klein KR, et al. Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.","where":"Lancet, 2026 (online 30 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42815506/","note":"2,749 randomised, 317 sites, median follow-up 2 years; MACE-4 hazard ratio 0.84 (95% CI 0.59–1.20), non-inferiority margin 1.8. NCT05803421."},{"cite":"FDA. Novel Drug Approvals for 2026 (Foundayo, orforglipron, approved 1 April 2026).","where":"FDA, read 7 Oct 2026","url":"https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026","note":"Approved use on the approval date: chronic weight management in adults with obesity, or overweight with a weight-related condition."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"ACHIEVE-4 (Lancet, 30 Sep 2026) added as a cardiovascular row: safety confirmed against insulin glargine, no reduction in events shown, graded B at effect 0. Status corrected to approved in the United States (Foundayo, FDA, 1 April 2026), which this page had not yet recorded. Other grades unchanged."},{"date":"2026-09-03","note":"Initial publication from the published phase 3 programme (ATTAIN-1, ACHIEVE-1, ATTAIN-2)."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"amycretin","name":"Amycretin","aliases":["Zenagamtide (INN)","GLP-1 and amylin co-agonist","unimolecular GLP-1/amylin receptor agonist"],"url":"https://lyoresearch.com/compounds/amycretin","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Amycretin is a single molecule that activates both the GLP-1 and the amylin receptor, combining the two mechanisms that CagriSema delivers as two drugs. Its international name is now zenagamtide. In the first published trial — a phase 1b/2a study in 125 people — the highest dose produced 24.3% weight loss at 36 weeks: the largest figure reported for any weight-loss drug at this stage, from a small, early trial in which many participants withdrew. Two phase 2 trials in type 2 diabetes, published in The Lancet in 2026, add a dose-dependent HbA1c reduction of up to 1.7 points; the weight-loss figure has not yet been repeated in a larger trial.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"1 phase 1b/2a RCT (n=125); 2 phase 2 RCTs in type 2 diabetes","regulatory_status":"Investigational (early phase)","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"No PubChem Compound record at review (investigational; zenagamtide)"},"pharmacokinetics":{"basis":"human","route":"Subcutaneous once weekly and oral once daily in the trials","half_life":"Dose-proportional exposure reported; no half-life figure in the accessible abstracts","licensed_regimen":null,"product":null,"source":{"title":"Gasiorek A, et al. Safety, tolerability, pharmacokinetics and pharmacodynamics of the first-in-class GLP-1 and amylin receptor agonist amycretin: a first-in-human phase 1 trial. Lancet 2025;406:135–148","url":"https://www.sciencedirect.com/science/article/abs/pii/S0140673625011766"}},"outcomes":[{"outcome":"Body weight","grade":"C","grade_meaning":"weak human evidence","effect_size":"large","adverse":false,"human_studies":"1 phase 1b/2a RCT (n=125)","evidence":"Doses were escalated over 20–36 weeks. At the top 60 mg dose, weight fell 24.3% against 1.1% on placebo. Substantial numbers of participants withdrew, mostly for reasons unrelated to side effects, which limits how much weight the figure carries.","references":[{"citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","where":"Lancet, 2025;406:149–162","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}],"verbatim":{"text":"Estimated mean bodyweight change from baseline was significantly (Parts A-D: p<0·0001; Part E: p=0·0003) higher with amycretin versus placebo in Part B (60 mg, -24·3% vs -1·1%; week 36), Part C (20 mg, -22·0% vs 1·9%; week 36), Part D (5 mg, -16·2% vs 2·3%; week 28), and Part E (1·25 mg, -9·7% vs 2·0%; week 20).","citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}},{"outcome":"Blood glucose (HbA1c) in type 2 diabetes","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 phase 2 RCT (n=262); oral companion trial","evidence":"A 36-week dose-finding trial of the weekly injection in adults with type 2 diabetes on metformin. HbA1c fell by 0.9 to 1.7 points across six doses, against placebo. A once-daily oral formulation was tested in a parallel trial. Both published in The Lancet, 2026.","references":[{"citation":"Mora P, et al. Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42532080/"},{"citation":"Mora P, et al. Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42532079/"}],"verbatim":{"text":"At week 36, estimated change in HbA1c (mean across all groups at baseline 7·8% [SD 0·8]) ranged from -0·9% with zenagamtide 0·4 mg (estimated treatment difference vs placebo: -0·77% [95% CI -1·26 to -0·28]; p=0·0021) to -1·7% with zenagamtide 40 mg (-1·56% [-2·05 to -1·07]; p<0·0001).","citation":"Mora P, et al. Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/42532080/"}},{"outcome":"Trial retention","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":true,"human_studies":"1 phase 1b/2a RCT","evidence":"The trial reports a high withdrawal rate. Because dropouts were largely for reasons unrelated to adverse events, the remaining participants may not represent everyone who started — the standard caution for an early-phase efficacy figure.","references":[{"citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","where":"Lancet, 2025;406:149–162","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}],"verbatim":{"text":"A large number of participants withdrew from the study, with a high proportion of discontinuations occurring due to reasons unrelated to treatment-emergent adverse events.","citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}},{"outcome":"GI side effects","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":true,"human_studies":"1 phase 1b/2a RCT","evidence":"Gastrointestinal events were frequent, as with every drug in this class, and mostly resolved.","references":[{"citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","where":"Lancet, 2025;406:149–162","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}],"verbatim":{"text":"The most common treatment-emergent adverse events were gastrointestinal, and the majority were mild to moderate in severity and resolved by the end of the study.","citation":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"Investigational; no EMA authorisation."},{"region":"United States","status":"Not approved","note":"Investigational. Products sold under this name are not the trial drug."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not named on the 2026 Prohibited List."}],"faq":[{"q":"Is amycretin really better than tirzepatide?","a":"Unknown. Its 24% figure comes from a phase 1b/2a trial in 125 people with heavy dropout; tirzepatide's 21% comes from a 2,539-person phase 3. Those are not comparable levels of evidence, and no head-to-head exists."},{"q":"How is it different from CagriSema?","a":"CagriSema is two molecules given together — cagrilintide plus semaglutide. Amycretin is one molecule doing both jobs."}],"references":[{"cite":"Dahl K, et al. Amycretin, a novel, unimolecular GLP-1 and amylin receptor agonist administered subcutaneously: results from a phase 1b/2a randomised controlled study.","where":"Lancet, 2025;406:149–162","url":"https://pubmed.ncbi.nlm.nih.gov/40550231/","note":"125 participants; up to 36 weeks. NCT06064006."},{"cite":"Mora P, et al. Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42532080/","note":"262 randomised, 36 weeks, six doses. NCT06542874."},{"cite":"Mora P, et al. Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42532079/","note":"Oral companion trial."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Name zenagamtide added. Two phase 2 trials in type 2 diabetes (Lancet, 2026) added with a verbatim primary result; new HbA1c row at B. Overall grade held at C: the weight-loss figure still rests on the 125-person early-phase trial."},{"date":"2026-09-03","note":"Initial publication from the phase 1b/2a Lancet report. Grade C for trial stage and retention."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"hgh","name":"Human growth hormone (somatropin)","aliases":["HGH","somatropin","rhGH","Genotropin","Norditropin","Humatrope"],"url":"https://lyoresearch.com/compounds/hgh","class":{"id":"growth-hormone-and-igf","name":"Growth hormone, IGF-1 and growth factors","url":"https://lyoresearch.com/classes/growth-hormone-and-igf"},"summary":"Growth hormone is a 191-amino-acid protein, approved for decades to treat genuine growth-hormone deficiency in children and adults, where it works well. Sold as an anti-ageing or physique drug, its record is different: a meta-analysis of randomised trials in healthy older adults found it shifts about 2 kg of fat to lean tissue with no change in total weight, while significantly raising rates of swelling, joint pain, carpal tunnel syndrome and gynaecomastia. The authors concluded it cannot be recommended for that purpose.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"Many RCTs + meta-analysis","regulatory_status":"Approved (Rx) for deficiency; anti-ageing use unlawful in the US","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"A 191-residue protein (somatropin) — no small-molecule record"},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, daily","half_life":"About 3 hours (subcutaneous)","licensed_regimen":"Paediatric GHD: 0.16-0.24 mg/kg/week SC; adult GHD: about 0.2 mg/day (0.15-0.30 mg/day), increased by 0.1-0.2 mg/day every 1-2 months","product":"Genotropin (somatropin)","source":{"title":"Genotropin prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ffebf88b-d257-4542-9808-74d9b7167765"}},"outcomes":[{"outcome":"Body composition in healthy older adults","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"Meta-analysis, 18 study populations","evidence":"Fat mass fell about 2.1 kg and lean mass rose about 2.1 kg, with no change in total body weight. A shift, not a loss — and smaller than most people expect.","references":[{"citation":"Liu H, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly.","where":"Ann Intern Med, 2007;146:104–115","url":"https://pubmed.ncbi.nlm.nih.gov/17227934/"}],"verbatim":{"text":"In participants treated with GH compared with those not treated with GH, overall fat mass decreased (change in fat mass, -2.1 kg [95% CI, -2.8 to -1.35] and overall lean body mass increased (change in lean body mass, 2.1 kg [CI, 1.3 to 2.9]) (P < 0.001), and their weight did not change significantly (change in weight, 0.1 kg [CI, -0.7 to 0.8]; P = 0.87).","citation":"Liu H, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly.","url":"https://pubmed.ncbi.nlm.nih.gov/17227934/"}},{"outcome":"Growth-hormone deficiency","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Approval-grade programmes","evidence":"In children and adults with diagnosed deficiency, replacement restores growth and improves body composition and quality of life. This is the licensed indication and is not in dispute.","references":[{"citation":"Somatropin prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Anti-ageing","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"No trial supports it","evidence":"No randomised trial has shown that growth hormone slows ageing or extends life in healthy people. The systematic review that examined the question concluded against the use.","references":[{"citation":"Liu H, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly.","where":"Ann Intern Med, 2007;146:104–115","url":"https://pubmed.ncbi.nlm.nih.gov/17227934/"}],"verbatim":{"text":"On the basis of this evidence, GH cannot be recommended as an antiaging therapy.","citation":"Liu H, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly.","url":"https://pubmed.ncbi.nlm.nih.gov/17227934/"}},{"outcome":"Adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"Meta-analysis","evidence":"Fluid retention, joint pain, carpal tunnel syndrome and breast tissue growth in men are all significantly more common, with a signal for new diabetes and impaired fasting glucose.","references":[{"citation":"Liu H, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly.","where":"Ann Intern Med, 2007;146:104–115","url":"https://pubmed.ncbi.nlm.nih.gov/17227934/"}],"verbatim":{"text":"Persons treated with GH were significantly more likely to experience soft tissue edema, arthralgias, carpal tunnel syndrome, and gynecomastia and were somewhat more likely to experience the onset of diabetes mellitus and impaired fasting glucose.","citation":"Liu H, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly.","url":"https://pubmed.ncbi.nlm.nih.gov/17227934/"}}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Multiple somatropin products authorised for growth-hormone deficiency and related indications. Supply for physique or anti-ageing use is outside the licence."},{"region":"United States","status":"Approved, prescription-only — anti-ageing distribution is a federal offence","note":"Approved for specific deficiency indications. Distributing growth hormone for anti-ageing or athletic use is expressly unlawful under US law, not merely off-label."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Licensed by the MHRA for deficiency indications."},{"region":"Australia","status":"Registered, prescription-only","note":"On the ARTG for deficiency indications; import without a prescription is an offence."},{"region":"Canada","status":"Authorised, prescription-only","note":"Authorised for deficiency indications."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Growth hormone is prohibited in and out of competition under the peptide-hormone class, and is specifically tested for."}],"faq":[{"q":"Does HGH build muscle in healthy adults?","a":"It increases lean body mass by roughly 2 kg on average in trials of older adults — but much of that is fluid, total weight does not change, and the trials did not show a matching gain in strength or function."},{"q":"Is HGH legal?","a":"As a prescription treatment for diagnosed deficiency, yes. In the United States, distributing it for anti-ageing or athletic purposes is a specific federal offence rather than ordinary off-label use."},{"q":"Why do so many peptides claim to raise growth hormone?","a":"Because raising it is easy to measure and sounds like a result. This page is the control experiment: give people the hormone itself and the effect on body composition is small and comes with side effects."}],"references":[{"cite":"Liu H, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly.","where":"Ann Intern Med, 2007;146:104–115","url":"https://pubmed.ncbi.nlm.nih.gov/17227934/","note":"18 study populations; the definitive assessment of anti-ageing use."},{"cite":"Somatropin prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/","note":"Licensed indications for growth-hormone deficiency."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Deficiency treatment graded A; anti-ageing use graded D on the systematic review."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"hcg","name":"HCG (human chorionic gonadotropin)","aliases":["human chorionic gonadotropin","Pregnyl","Ovidrel","chorionic gonadotropin alfa"],"url":"https://lyoresearch.com/compounds/hcg","class":{"id":"reproductive-hormones","name":"Reproductive and neuroendocrine hormones","url":"https://lyoresearch.com/classes/reproductive-hormones"},"summary":"HCG is a hormone of pregnancy, approved to trigger ovulation in fertility treatment and to treat certain forms of low testosterone and undescended testicles. It is also the basis of the HCG diet, which pairs injections with a 500-calorie regime. A meta-analysis of the controlled trials found no evidence that HCG does anything at all for weight, hunger or fat distribution — any weight lost is caused by the starvation diet accompanying it.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"Approval-grade + meta-analysis","regulatory_status":"Approved (Rx) for fertility and hypogonadism; not for weight loss","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"A glycoprotein hormone (two subunits, glycosylated) — no small-molecule record"},"pharmacokinetics":{"basis":"label","route":"Intramuscular injection","half_life":"Not stated in the label","licensed_regimen":"Hypogonadotropic hypogonadism: 500-1,000 USP units three times weekly for 3 weeks then twice weekly for 3 weeks, or 4,000 USP units three times weekly for 6-9 months; ovulation induction: 5,000-10,000 USP units one day after the last gonadotropin dose","product":"Pregnyl (chorionic gonadotropin)","source":{"title":"Pregnyl prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=1e94155f-19be-4944-b197-be4edbb4faf9"}},"outcomes":[{"outcome":"Ovulation induction and fertility","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Approval-grade programmes","evidence":"Triggering final oocyte maturation is HCG's licensed use and standard practice in assisted reproduction worldwide.","references":[{"citation":"Chorionic gonadotropin prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Testosterone stimulation in men","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Approval-grade","evidence":"Licensed for hypogonadotropic hypogonadism, where it stimulates the testes directly; used clinically to maintain testicular function and fertility.","references":[{"citation":"Chorionic gonadotropin prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Weight loss","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"Meta-analysis of 8 controlled trials","evidence":"Repeatedly tested against placebo alongside the same very-low-calorie diet. The diet produces the weight loss; HCG adds nothing measurable to weight, hunger, fat distribution or wellbeing.","references":[{"citation":"Lijesen GKS, et al. The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis.","where":"Br J Clin Pharmacol, 1995;40:237–243","url":"https://pubmed.ncbi.nlm.nih.gov/8527285/"}],"verbatim":{"text":"We conclude that there is no scientific evidence that HCG is effective in the treatment of obesity; it does not bring about weight-loss of fat-redistribution, nor does it reduce hunger or induce a feeling of well-being.","citation":"Lijesen GKS, et al. The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis.","url":"https://pubmed.ncbi.nlm.nih.gov/8527285/"}}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Authorised for fertility indications and hypogonadotropic hypogonadism."},{"region":"United States","status":"Approved, prescription-only — weight-loss use prohibited on the label","note":"FDA-approved for fertility and hypogonadism. Labelling must state that HCG has no proven effect on weight loss, fat distribution or hunger; homeopathic and over-the-counter 'HCG diet' products are unapproved and have been the subject of enforcement."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Licensed for fertility indications."},{"region":"Australia","status":"Registered, prescription-only","note":"On the ARTG for fertility and hypogonadism."},{"region":"Canada","status":"Authorised, prescription-only","note":"Authorised for fertility indications."},{"region":"Sport (WADA)","status":"Prohibited in males at all times","note":"Prohibited for male athletes as a testosterone-stimulating agent."}],"faq":[{"q":"Does the HCG diet work?","a":"The 500-calorie diet works; the injections do not add anything. In controlled trials HCG produced no more weight loss, no less hunger and no different fat distribution than placebo. Losing weight on 500 calories a day is not evidence that the hormone did it."},{"q":"Is HCG legal?","a":"Yes, as a prescription medicine for fertility and hypogonadism. Over-the-counter and homeopathic 'HCG diet' products are unapproved, and in the US the label must state it has no proven weight-loss effect."},{"q":"Is HCG used with testosterone therapy?","a":"It is prescribed clinically to preserve testicular function and fertility during testosterone therapy. That is a decision for a clinician and outside what this site covers."}],"references":[{"cite":"Lijesen GKS, et al. The effect of human chorionic gonadotropin (HCG) in the treatment of obesity by means of the Simeons therapy: a criteria-based meta-analysis.","where":"Br J Clin Pharmacol, 1995;40:237–243","url":"https://pubmed.ncbi.nlm.nih.gov/8527285/","note":"8 controlled and 16 uncontrolled trials."},{"cite":"Chorionic gonadotropin prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/","note":"Fertility and hypogonadism indications; required weight-loss disclaimer."},{"cite":"Young RL, et al. Chorionic gonadotropin in weight control: a double-blind crossover study.","where":"JAMA, 1976","url":"https://pubmed.ncbi.nlm.nih.gov/792477/"}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Fertility and hypogonadism graded A; weight loss graded A for a well-established absence of effect."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"glutathione","name":"Glutathione","aliases":["GSH","reduced glutathione","L-glutathione","IV glutathione"],"url":"https://lyoresearch.com/compounds/glutathione","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"Glutathione is a three-amino-acid molecule every cell makes and uses to handle oxidative stress. It is sold orally and, in some countries, intravenously for skin lightening. Systematic reviews of the small trials find it may brighten sun-exposed skin slightly, but call the evidence inconclusive because the studies are few, small and inconsistent. Oral absorption is itself questionable, and the intravenous use that carries the most risk has the least evidence — in 2026 the FDA linked at least 30 adverse events, some needing hospital care, to injectables compounded from supplement-grade glutathione contaminated with endotoxin.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Small RCTs; systematic reviews inconclusive","regulatory_status":"Supplement; injectable use unapproved","molecule":{"formula":"C10H17N3O6S","molecular_weight":"307.33","cas":"70-18-8","pubchem_cid":124886,"note":null},"pharmacokinetics":{"basis":"human","route":"Intravenous in the PK study; oral supplements have negligible bioavailability","half_life":"About 14 minutes (intravenous, healthy volunteers). A 3 g oral dose did not raise plasma glutathione","licensed_regimen":null,"product":null,"source":{"title":"Aebi S, et al. High-dose intravenous glutathione in man: pharmacokinetics and effects on cyst(e)ine in plasma and urine. Eur J Clin Invest 1991","url":"https://pubmed.ncbi.nlm.nih.gov/1907548/"}},"outcomes":[{"outcome":"Skin lightening","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"4 studies in systematic review (3 RCTs)","evidence":"Oral 500 mg/day and topical 2% oxidised glutathione reduced the melanin index in sun-exposed skin; no effect was seen in sun-protected skin. Reviewers judged the overall evidence inconclusive.","references":[{"citation":"Dilokthornsakul W, et al. The clinical effect of glutathione on skin color and other related skin conditions: a systematic review.","where":"J Cosmet Dermatol, 2019;18:728–737","url":"https://pubmed.ncbi.nlm.nih.gov/30895708/"}],"verbatim":{"text":"Current evidence of the skin whitening effect of glutathione is still inconclusive due to the quality of included studies and inconsistent findings.","citation":"Dilokthornsakul W, et al. The clinical effect of glutathione on skin color and other related skin conditions: a systematic review.","url":"https://pubmed.ncbi.nlm.nih.gov/30895708/"}},{"outcome":"Oral bioavailability","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":true,"human_studies":"Reviews","evidence":"Whether swallowed glutathione survives digestion in a useful form is unresolved, and is the standing objection to the oral products.","references":[{"citation":"Dilokthornsakul W, et al. The clinical effect of glutathione on skin color and other related skin conditions: a systematic review.","where":"J Cosmet Dermatol, 2019;18:728–737","url":"https://pubmed.ncbi.nlm.nih.gov/30895708/"}],"verbatim":{"text":"However, the clinical efficacy of glutathione in oral form is still questionable due to its limited absorption and bioavailability.","citation":"Dilokthornsakul W, et al. The clinical effect of glutathione on skin color and other related skin conditions: a systematic review.","url":"https://pubmed.ncbi.nlm.nih.gov/30895708/"}},{"outcome":"Intravenous use for skin","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"No adequate controlled trial","evidence":"The intravenous route is the one most heavily marketed and the least studied. Regulators in several countries have warned against it, and injecting an unapproved product carries risks the skin trials never measured.","references":[{"citation":"Sarkar R, et al. Glutathione as a skin-lightening agent and in melasma: a systematic review.","where":"Int J Dermatol, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/39444151/"}]},{"outcome":"Endotoxin reactions from compounded injectables","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":true,"human_studies":"FDA case series (≥30 patients); recalls","evidence":"On 27 August 2026 the FDA reported at least 30 patients with fever, chills, pain, dizziness and shock-like symptoms after intravenous glutathione compounded from dietary-supplement-grade material, some hospitalised, and judged the picture consistent with excess endotoxin. A nationwide recall of affected lots followed in September, with nine further reports, and on 1 October 2026 another compounding pharmacy recalled ten lots after two patients needed emergency care; both had been given intravenously a product made for injection under the skin. Not a trial, but a regulator-verified harm signal for the injectable route.","references":[{"citation":"FDA. FDA reminds compounders not to use dietary supplement-grade glutathione in injectables.","where":"FDA statement, 27 Aug 2026","url":"https://www.fda.gov/drugs/human-drug-compounding/fda-reminds-compounders-not-use-dietary-supplement-grade-glutathione-injectables"},{"citation":"FDA. Nationwide recall of compounded glutathione injectables and two blends due to elevated endotoxin levels.","where":"FDA recall notice, posted 13 Sep 2026","url":"https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/centric-compounding-issues-nationwide-recall-glutathione-myers-cocktail-and-tri-immune-boost-due"},{"citation":"FDA. Voluntary nationwide recall of compounded glutathione injection due to potential elevated endotoxin levels (company announcement).","where":"FDA recall notice, 1 Oct 2026","url":"https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/greenwich-rx-issues-voluntary-nationwide-recall-compounded-glutathione-due-elevated-endotoxin-levels"}]},{"outcome":"Safety (oral, short-term)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":true,"human_studies":"Small trials","evidence":"Short-term oral use was tolerated in the trials, with non-serious adverse events reported. Long-term and injectable safety are not established.","references":[{"citation":"Dilokthornsakul W, et al. The clinical effect of glutathione on skin color and other related skin conditions: a systematic review.","where":"J Cosmet Dermatol, 2019;18:728–737","url":"https://pubmed.ncbi.nlm.nih.gov/30895708/"}],"verbatim":{"text":"Some adverse events but nonserious were reported.","citation":"Dilokthornsakul W, et al. The clinical effect of glutathione on skin color and other related skin conditions: a systematic review.","url":"https://pubmed.ncbi.nlm.nih.gov/30895708/"}}],"regions":[{"region":"European Union","status":"Supplement; injectable unapproved","note":"Sold as a food supplement. No authorised injectable product for cosmetic use."},{"region":"United States","status":"Supplement; injectable unapproved","note":"Oral products sold as dietary supplements. Injectable glutathione is not FDA-approved. In August 2026 the FDA reminded compounders not to make injectables from supplement-grade glutathione after at least 30 endotoxin-type reactions, and a nationwide recall of contaminated lots followed in September. Another recall of ten lots followed on 1 October 2026, after two patients needed emergency care."},{"region":"United Kingdom","status":"Supplement","note":"Oral supplement; injectable cosmetic use is unlicensed."},{"region":"Australia","status":"Complementary medicine","note":"Oral listed products; injectable cosmetic use is not registered."},{"region":"Canada","status":"Natural health product","note":"Oral products may carry an NPN; injectable cosmetic use is not authorised."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the 2026 Prohibited List. Intravenous infusions above the permitted volume are separately restricted regardless of what is infused."}],"faq":[{"q":"Does glutathione lighten skin?","a":"Possibly, slightly, in sun-exposed areas — but the systematic reviews call the evidence inconclusive because the trials are few, small and inconsistent. It is not an established treatment."},{"q":"Is IV glutathione safe?","a":"It is the least studied and most heavily marketed route. There is no adequate controlled trial of it for skin, and in 2026 the FDA linked at least 30 adverse events — fever, chills, shock-like symptoms, some hospitalised — to injectables compounded from supplement-grade glutathione contaminated with endotoxin."},{"q":"Is glutathione a peptide?","a":"Yes — a tripeptide of glutamate, cysteine and glycine, though an unusual one, joined through an atypical bond."}],"references":[{"cite":"Dilokthornsakul W, et al. The clinical effect of glutathione on skin color and other related skin conditions: a systematic review.","where":"J Cosmet Dermatol, 2019;18:728–737","url":"https://pubmed.ncbi.nlm.nih.gov/30895708/","note":"4 studies; conclusion inconclusive."},{"cite":"Sarkar R, et al. Glutathione as a skin-lightening agent and in melasma: a systematic review.","where":"Int J Dermatol, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/39444151/"},{"cite":"Arjinpathana N, Asawanonda P. Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study.","where":"J Dermatolog Treat, 2012","url":"https://pubmed.ncbi.nlm.nih.gov/20524875/"},{"cite":"FDA. FDA reminds compounders not to use dietary supplement-grade glutathione in injectables.","where":"FDA statement, 27 Aug 2026","url":"https://www.fda.gov/drugs/human-drug-compounding/fda-reminds-compounders-not-use-dietary-supplement-grade-glutathione-injectables","note":"At least 30 patients; symptoms consistent with excessive endotoxin; some hospitalised."},{"cite":"FDA. Nationwide recall of compounded glutathione injectables and two blends due to elevated endotoxin levels.","where":"FDA recall notice, posted 13 Sep 2026","url":"https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/centric-compounding-issues-nationwide-recall-glutathione-myers-cocktail-and-tri-immune-boost-due","note":"Three glutathione 200 mg/mL lots plus blends made with the same material; nine reports of fever, chills, chest pain, nausea, headache or malaise."},{"cite":"FDA. Voluntary nationwide recall of compounded glutathione injection due to potential elevated endotoxin levels (company announcement).","where":"FDA recall notice, 1 Oct 2026","url":"https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/greenwich-rx-issues-voluntary-nationwide-recall-compounded-glutathione-due-elevated-endotoxin-levels","note":"Ten lots of glutathione 200 mg/mL, distributed 26 June to 21 September 2026; two reports of emergency care after intravenous use of a product intended for subcutaneous injection."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"A further US recall of compounded glutathione injection for potential endotoxin (1 Oct 2026, ten lots, two emergency-care reports) added to the endotoxin row and the US status. Grades unchanged."},{"date":"2026-09-23","note":"FDA endotoxin cases (27 Aug 2026) and the September recall added as an adverse-effect row and to the US status. Grades otherwise unchanged."},{"date":"2026-09-03","note":"Initial publication. Grade C on small, inconsistent trials; intravenous cosmetic use graded D."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"igf-1-lr3","name":"IGF-1 LR3","aliases":["Long R3 IGF-1","LR3 IGF-1","insulin-like growth factor 1 analogue"],"url":"https://lyoresearch.com/compounds/igf-1-lr3","class":{"id":"growth-hormone-and-igf","name":"Growth hormone, IGF-1 and growth factors","url":"https://lyoresearch.com/classes/growth-hormone-and-igf"},"summary":"IGF-1 LR3 is a modified version of insulin-like growth factor 1, engineered so that it evades the binding proteins that normally control IGF-1 and therefore stays active far longer. It was designed as a cell-culture reagent for laboratories, not as a medicine, and no controlled human trial has ever tested it. Natural IGF-1 is available as an approved drug, mecasermin, for a rare severe deficiency — the LR3 analogue is a different molecule with no clinical file at all.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 controlled","regulatory_status":"Not approved; research reagent","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"An 83-residue protein analogue; not in PubChem Compound at review"},"pharmacokinetics":{"basis":"none","route":"Injected as sold; no human study (mecasermin is a different, approved product)","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Muscle growth","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"No controlled human trial of IGF-1 LR3 exists for muscle, strength or body composition. The claims extrapolate from IGF-1's known role in tissue growth and from animal and cell work.","references":[]},{"outcome":"Any clinical outcome","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"A PubMed search for the compound and its aliases returns recombinant-expression papers, rodent studies and reviews of self-administration — no human trial.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None","evidence":"No human dosing study exists. The theoretical concerns are hypoglycaemia, because IGF-1 has insulin-like activity, and the long-term effect of sustained growth signalling — neither measured in people for this analogue.","references":[{"citation":"Dominikowski A, et al. The emerging landscape of performance-enhancing peptides modulating the GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration.","where":"Front Endocrinol, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42395176/"}]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation. Sold as a research reagent; supplying it for human use is an offence under national medicines law."},{"region":"United States","status":"Not approved","note":"Not an approved drug. Mecasermin (recombinant human IGF-1) is approved for severe primary IGF-1 deficiency; the LR3 analogue is a different, unapproved molecule."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence; supply for human use is an offence."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"IGF-1 and its analogues are prohibited in and out of competition as growth factors."}],"faq":[{"q":"Does IGF-1 LR3 build muscle?","a":"No controlled human trial has tested it. Every claim rests on IGF-1's known biology and on animal work, not on evidence in people."},{"q":"Is it the same as the approved IGF-1 drug?","a":"No. Mecasermin is recombinant human IGF-1, approved for a rare severe deficiency. LR3 is a modified analogue built to evade the body's control mechanisms, and it has no approval or clinical trial anywhere."},{"q":"Why is it sold as 'research use only'?","a":"Because that is what it was made for — a cell-culture reagent. The label is not a loophole that makes human use lawful or studied."}],"references":[{"cite":"Dominikowski A, et al. The emerging landscape of performance-enhancing peptides modulating the GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration.","where":"Front Endocrinol, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42395176/","note":"Review of the gap between evidence and self-administration in this class."},{"cite":"Mecasermin (Increlex) prescribing information — recombinant human IGF-1 for severe primary IGF-1 deficiency.","where":"FDA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/","note":"The approved IGF-1 product, for contrast."}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. All outcomes graded D on the absence of any human trial of the LR3 analogue."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"dsip","name":"DSIP (delta sleep-inducing peptide)","aliases":["delta sleep-inducing peptide","DSIP","Trp-Ala-Gly-Gly-Asp-Ala-Ser-Gly-Glu"],"url":"https://lyoresearch.com/compounds/dsip","class":{"id":"nootropic-peptides","name":"Nootropic and sleep peptides","url":"https://lyoresearch.com/classes/nootropic-peptides"},"summary":"DSIP is a nine-amino-acid peptide isolated from rabbit brain in the 1970s and named for the sleep pattern it appeared to induce. Unusually for a grey-market sleep peptide, it was tested in people: several small studies in chronic insomnia through the 1980s and 90s. The best-controlled of them found effects that were weak, possibly artefactual, and concluded it was unlikely to be of major therapeutic benefit. Development stopped.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Several small trials, 1981–1998","regulatory_status":"Not approved","molecule":{"formula":"C35H48N10O15","molecular_weight":"848.8","cas":"62568-57-4","pubchem_cid":68816,"note":null},"pharmacokinetics":{"basis":"none","route":"Intravenous in the 1980s sleep studies, which report no PK","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Sleep in chronic insomnia","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 double-blind RCT (n=16) + small studies","evidence":"Intravenous DSIP improved measured sleep efficiency and latency against placebo, but the authors judged the effects weak and partly attributable to a change in the placebo group, with no improvement in how patients rated their own sleep.","references":[{"citation":"Bes F, et al. Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients: a double-blind study.","where":"Neuropsychobiology, 1992;26:193–197","url":"https://pubmed.ncbi.nlm.nih.gov/1299794/"}],"verbatim":{"text":"Data analysis suggested, however, that the statistically significant effects were weak and in part could be due to an incidental change in the placebo group. As none of the other measures, including subjective sleep quality, showed any change, it was concluded that short-term treatment of chronic insomnia with DSIP is not likely to be of major therapeutic benefit.","citation":"Bes F, et al. Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients: a double-blind study.","url":"https://pubmed.ncbi.nlm.nih.gov/1299794/"}},{"outcome":"Opioid withdrawal","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 open trial","evidence":"An open-label study in opioid detoxification was published in 1998. Without a control group it cannot separate the peptide from the natural course of withdrawal, and it was not followed up.","references":[{"citation":"Backmund M, et al. Opioid detoxification with delta sleep-inducing peptide: results of an open clinical trial.","where":"J Clin Psychopharmacol, 1998","url":"https://pubmed.ncbi.nlm.nih.gov/9617990/"}]},{"outcome":"Recovery, stress or performance","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"The recovery and anti-stress claims made for DSIP today have no controlled human trial behind them.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"No systematic data","evidence":"The old studies were small and short, and none was designed to characterise safety. There is no modern safety dataset at the doses and routes used on the grey market.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state; supplying it for human use is an offence under national medicines law."},{"region":"United States","status":"Not approved","note":"Not an approved drug and not a dietary-supplement ingredient; sold as a research chemical."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence; supply for human use is an offence."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"As a non-approved substance it falls under the non-approved-substances class and is prohibited in and out of competition."}],"faq":[{"q":"Does DSIP help you sleep?","a":"The best-controlled trial found weak effects on measured sleep, no change in how patients rated their own sleep, and concluded it was unlikely to be of major therapeutic benefit. That is a genuine negative result rather than an absence of evidence."},{"q":"Why is it still sold if the trials were negative?","a":"The trials are forty years old, small, and largely forgotten outside the literature. The name — 'delta sleep-inducing peptide' — does a great deal of marketing work on its own."},{"q":"Is DSIP safe?","a":"Unknown. The old studies were too small and too short to characterise safety, and there is no modern data at the doses sold today."}],"references":[{"cite":"Bes F, et al. Effects of delta sleep-inducing peptide on sleep of chronic insomniac patients: a double-blind study.","where":"Neuropsychobiology, 1992;26:193–197","url":"https://pubmed.ncbi.nlm.nih.gov/1299794/","note":"16 patients; the best-controlled trial."},{"cite":"Backmund M, et al. Opioid detoxification with delta sleep-inducing peptide: results of an open clinical trial.","where":"J Clin Psychopharmacol, 1998","url":"https://pubmed.ncbi.nlm.nih.gov/9617990/","note":"Open-label, no control group."},{"cite":"Schneider-Helmert D, et al. Acute and delayed effects of DSIP on human sleep behavior.","where":"Int J Clin Pharmacol Ther Toxicol, 1981","url":"https://pubmed.ncbi.nlm.nih.gov/6895513/"}],"last_reviewed":"2026-09-03","literature_searched_to":"2026-09-03","changelog":[{"date":"2026-09-03","note":"Initial publication. Sleep graded C on small trials with a negative conclusion; other claims graded D."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"mk-677","name":"MK-677 (ibutamoren)","aliases":["ibutamoren","ibutamoren mesylate","MK-0677","Nutrobal","L-163,191"],"url":"https://lyoresearch.com/compounds/mk-677","class":{"id":"gh-secretagogues","name":"GH secretagogues (GHRPs)","url":"https://lyoresearch.com/classes/gh-secretagogues"},"summary":"MK-677 is a small molecule, not a peptide, that mimics the hunger hormone ghrelin and raises growth hormone and IGF-1 when taken by mouth. Unusually for a grey-market compound, it has been through proper trials. In 65 healthy older adults over a year it raised fat-free mass by about 1.1 kg against a 0.5 kg loss on placebo, with no change in total or visceral fat. In 563 people with Alzheimer's disease it raised IGF-1 by 73% and did nothing for the disease. It has never been approved anywhere and is prohibited in sport.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"2 large RCTs (n=65 over 2 yr; n=563 over 1 yr) + small studies","regulatory_status":"Not approved","molecule":{"formula":"C27H36N4O5S","molecular_weight":"528.7","cas":"159634-47-6","pubchem_cid":178024,"note":null},"pharmacokinetics":{"basis":"human","route":"Oral, once daily in the trials","half_life":"Taken by mouth daily in year-long trials; no primary half-life figure was found in the accessible literature (the '24 hours' repeated online could not be traced to a source)","licensed_regimen":null,"product":null,"source":{"title":"Copinschi G, et al. Effects of a 7-day treatment with a novel, orally active, growth hormone secretagogue, MK-677, in normal young men. J Clin Endocrinol Metab 1996;81:2776","url":"https://pubmed.ncbi.nlm.nih.gov/8768828/"}},"outcomes":[{"outcome":"Growth hormone / IGF-1 elevation","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Multiple RCTs","evidence":"Oral daily dosing reliably restores growth hormone and IGF-1 in older adults to the levels of healthy young adults, and raised IGF-1 by 60–73% in a 563-person trial. This effect is not in dispute.","references":[{"citation":"Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.","where":"Ann Intern Med, 2008;149(9):601–611","url":"https://pubmed.ncbi.nlm.nih.gov/18981485/"},{"citation":"Sevigny JJ, Ryan JM, Van Dyck CH, et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.","where":"Neurology, 2008","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sevigny+MK-677+Alzheimer+disease+progression+randomized+2008"}],"verbatim":{"text":"Daily administration of MK-677 significantly increased growth hormone and insulin-like growth factor I levels to those of healthy young adults without serious adverse effects.","citation":"Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.","url":"https://pubmed.ncbi.nlm.nih.gov/18981485/"}},{"outcome":"Lean mass (older adults)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":false,"human_studies":"1 RCT (n=65, 12 months)","evidence":"Fat-free mass rose by about 1.1 kg over a year against a 0.5 kg loss on placebo — a real difference, in one trial, in people over 60. Whether that becomes strength or function was not shown; the authors themselves called for functional studies.","references":[{"citation":"Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.","where":"Ann Intern Med, 2008;149(9):601–611","url":"https://pubmed.ncbi.nlm.nih.gov/18981485/"}],"verbatim":{"text":"Mean fat-free mass decreased in the placebo group but increased in the MK-677 group (change, -0.5 kg [95% CI, -1.1 to 0.2 kg] vs. 1.1 kg [CI, 0.7 to 1.5 kg], respectively; P < 0.001), as did body cell mass, as reflected by intracellular water (change, -1.0 kg [CI, -2.1 to 0.2 kg] vs. 0.8 kg [CI, -0.1 to 1.6 kg], respectively; P = 0.021).","citation":"Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.","url":"https://pubmed.ncbi.nlm.nih.gov/18981485/"}},{"outcome":"Fat loss","grade":"B","grade_meaning":"probable, not settled","effect_size":"not measurable","adverse":false,"human_studies":"1 RCT (n=65) — no effect","evidence":"Neither total fat mass nor abdominal visceral fat changed over a year; limb fat actually rose more on MK-677 than on placebo. Sold for fat loss, it did the opposite in the one trial that measured it.","references":[{"citation":"Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.","where":"Ann Intern Med, 2008;149(9):601–611","url":"https://pubmed.ncbi.nlm.nih.gov/18981485/"}],"verbatim":{"text":"No significant differences were observed in abdominal visceral fat or total fat mass; however, the average increase in limb fat was greater in the MK-677 group than the placebo group (1.1 kg vs. 0.24 kg; P = 0.001).","citation":"Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.","url":"https://pubmed.ncbi.nlm.nih.gov/18981485/"}},{"outcome":"Alzheimer's disease progression","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"1 RCT (n=563, 12 months) — negative","evidence":"A year of 25 mg daily in mild-to-moderate Alzheimer's raised IGF-1 substantially and changed none of the four clinical measures. A clean negative: the target was engaged, and it made no difference.","references":[{"citation":"Sevigny JJ, Ryan JM, Van Dyck CH, et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.","where":"Neurology, 2008","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sevigny+MK-677+Alzheimer+disease+progression+randomized+2008"}],"verbatim":{"text":"Despite evidence of target engagement as indicated by an increase in serum insulin-like growth factor-1, the human growth hormone secretagogue MK-677 25 mg was ineffective at slowing the rate of progression of Alzheimer disease.","citation":"Sevigny JJ, Ryan JM, Van Dyck CH, et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sevigny+MK-677+Alzheimer+disease+progression+randomized+2008"}},{"outcome":"Adverse effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":true,"human_studies":"Same RCTs","evidence":"Increased appetite, fluid retention and oedema, muscle pain, and rises in fasting glucose and insulin resistance are reported consistently, as with any sustained growth-hormone elevation. The trials were one to two years; there is no data beyond that.","references":[{"citation":"Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.","where":"Ann Intern Med, 2008;149(9):601–611","url":"https://pubmed.ncbi.nlm.nih.gov/18981485/"},{"citation":"Sevigny JJ, Ryan JM, Van Dyck CH, et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.","where":"Neurology, 2008","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sevigny+MK-677+Alzheimer+disease+progression+randomized+2008"}]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Supplying it for human use is an offence under national medicines law."},{"region":"United States","status":"Not approved","note":"Never approved; development discontinued. Sold as a 'research chemical'. Not a lawful dietary-supplement ingredient."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence; supply for human use is an offence."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Named on the Prohibited List among growth-hormone secretagogues, in and out of competition."}],"faq":[{"q":"Does MK-677 build muscle?","a":"In the one year-long trial, fat-free mass rose by about 1.1 kg in older adults against a loss on placebo. That is lean tissue, which includes water, and the trial did not measure strength. In young, trained people it has never been tested."},{"q":"Does MK-677 burn fat?","a":"No. Total fat and visceral fat did not change over a year, and limb fat rose. The appetite increase that comes with a ghrelin mimic works against fat loss."},{"q":"Is MK-677 a peptide?","a":"No — it is a small molecule designed to do what the ghrelin-mimicking peptides do, but by mouth. It is covered here because it is sold alongside them and acts on the same receptor."},{"q":"Is MK-677 legal?","a":"It is not an approved medicine anywhere and is prohibited in sport at all times. Rules on possession vary by country; selling it for human use is an offence in the EU and UK."}],"references":[{"cite":"Nass R, Pezzoli SS, Oliveri MC, et al. Effects of an oral ghrelin mimetic on body composition and clinical outcomes in healthy older adults: a randomized trial.","where":"Ann Intern Med, 2008;149(9):601–611","url":"https://pubmed.ncbi.nlm.nih.gov/18981485/","note":"65 adults aged 60–81; two years, primary analysis at one year."},{"cite":"Sevigny JJ, Ryan JM, Van Dyck CH, et al. Growth hormone secretagogue MK-677: no clinical effect on AD progression in a randomized trial.","where":"Neurology, 2008","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Sevigny+MK-677+Alzheimer+disease+progression+randomized+2008","note":"563 patients; 12 months; negative on all four clinical measures."},{"cite":"World Anti-Doping Agency. The Prohibited List — S2: peptide hormones, growth factors, related substances and mimetics.","where":"WADA, current list","url":"https://www.wada-ama.org/en/prohibited-list","note":"Growth-hormone secretagogues, ibutamoren named."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade B for lean mass on one 12-month RCT; fat loss and Alzheimer's carry high-certainty null results (effect none)."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"dulaglutide","name":"Dulaglutide","aliases":["Trulicity","LY2189265","GLP-1 receptor agonist"],"url":"https://lyoresearch.com/compounds/dulaglutide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Dulaglutide is a once-weekly GLP-1 receptor agonist made of two GLP-1 analogue chains fused to an antibody fragment, approved for type 2 diabetes since 2014. In the 9,901-person REWIND trial it reduced major cardiovascular events by 12% relative to placebo over 5.4 years in people with diabetes, most of whom had no prior heart disease. It is not approved for weight management and produces modest weight loss — a few kilograms — well below semaglutide or tirzepatide. It is prescription-only everywhere it is sold.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"REWIND (n=9,901) + AWARD programme","regulatory_status":"Approved (Rx)","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"A fusion protein (two GLP-1 analogue chains on an antibody Fc fragment) — no small-molecule record"},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, once weekly","half_life":"About 5 days","licensed_regimen":"0.75 mg weekly; after 4 weeks increase to 1.5 mg weekly; may increase in 1.5 mg increments after at least 4 weeks; maximum 4.5 mg weekly","product":"Trulicity","source":{"title":"Trulicity prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=463050bd-2b1c-40f5-b3c3-0a04bb433309"}},"outcomes":[{"outcome":"Major cardiovascular events (type 2 diabetes)","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"1 large RCT (n=9,901, median 5.4 yr)","evidence":"Twelve percent fewer heart attacks, strokes and cardiovascular deaths than placebo, in a population where two-thirds had risk factors but no prior cardiovascular disease — the broadest such population of any GLP-1 outcomes trial.","references":[{"citation":"Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.","where":"Lancet, 2019","url":"https://pubmed.ncbi.nlm.nih.gov/31189511/"}],"verbatim":{"text":"During a median follow-up of 5·4 years (IQR 5·1-5·9), the primary composite outcome occurred in 594 (12·0%) participants at an incidence rate of 2·4 per 100 person-years in the dulaglutide group and in 663 (13·4%) participants at an incidence rate of 2·7 per 100 person-years in the placebo group (hazard ratio [HR] 0·88, 95% CI 0·79-0·99; p=0·026).","citation":"Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/31189511/"}},{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"AWARD programme (10+ RCTs)","evidence":"Approval-grade reductions in HbA1c across the AWARD trials against placebo and active comparators; the licensed indication.","references":[{"citation":"Dulaglutide (Trulicity) product information and the AWARD clinical programme.","where":"FDA / EMA product information","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/trulicity"}]},{"outcome":"Body weight","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"AWARD programme","evidence":"Consistent but modest weight loss of a few kilograms at the diabetes doses; higher doses (3 mg, 4.5 mg) add a little more. It is not approved for weight management and is not comparable to semaglutide 2.4 mg or tirzepatide.","references":[{"citation":"Dulaglutide (Trulicity) product information and the AWARD clinical programme.","where":"FDA / EMA product information","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/trulicity"}]},{"outcome":"All-cause mortality","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"REWIND","evidence":"Deaths from any cause were numerically lower but the difference was not statistically significant.","references":[{"citation":"Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.","where":"Lancet, 2019","url":"https://pubmed.ncbi.nlm.nih.gov/31189511/"}],"verbatim":{"text":"All-cause mortality did not differ between groups (536 [10·8%] in the dulaglutide group vs 592 [12·0%] in the placebo group; HR 0·90, 95% CI 0·80-1·01; p=0·067).","citation":"Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/31189511/"}},{"outcome":"Gastrointestinal adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"REWIND","evidence":"Nearly half of participants reported a gastrointestinal adverse event over the trial, against a third on placebo — the class profile.","references":[{"citation":"Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.","where":"Lancet, 2019","url":"https://pubmed.ncbi.nlm.nih.gov/31189511/"}],"verbatim":{"text":"2347 (47·4%) participants assigned to dulaglutide reported a gastrointestinal adverse event during follow-up compared with 1687 (34·1%) participants assigned to placebo (p<0·0001).","citation":"Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/31189511/"}}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Centrally authorised (Trulicity) for type 2 diabetes since 2014."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved 2014 for type 2 diabetes; 2020 for cardiovascular risk reduction in type 2 diabetes."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"MHRA-licensed for type 2 diabetes."},{"region":"Australia","status":"Registered, prescription-only","note":"On the ARTG for type 2 diabetes."},{"region":"Canada","status":"Authorised, prescription-only","note":"Health Canada-authorised for type 2 diabetes."},{"region":"Sport (WADA)","status":"Not prohibited","note":"GLP-1 receptor agonists are not on the Prohibited List."}],"faq":[{"q":"Is dulaglutide good for weight loss?","a":"It causes modest weight loss — a few kilograms at diabetes doses — and is not approved for weight management. Semaglutide 2.4 mg and tirzepatide produce several times more."},{"q":"Does dulaglutide protect the heart?","a":"In REWIND, yes: 12% fewer major cardiovascular events over 5.4 years in people with type 2 diabetes, including those with risk factors but no prior heart disease. Deaths overall were not significantly reduced."},{"q":"Dulaglutide or semaglutide?","a":"Both are weekly GLP-1 drugs with cardiovascular-outcome evidence in diabetes. Semaglutide produces much larger weight loss, has an obesity approval, and has an outcomes trial in obesity without diabetes; dulaglutide's outcomes trial covered the broader diabetes population. The comparison is a prescribing decision outside what this site covers."}],"references":[{"cite":"Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial.","where":"Lancet, 2019","url":"https://pubmed.ncbi.nlm.nih.gov/31189511/","note":"9,901 participants; median 5.4 years; HR 0.88."},{"cite":"Dulaglutide (Trulicity) product information and the AWARD clinical programme.","where":"FDA / EMA product information","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/trulicity","note":"Licensed indications and the glucose and weight data behind them."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade A on REWIND and the AWARD programme."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"exenatide","name":"Exenatide","aliases":["Byetta","Bydureon","exendin-4","AC2993"],"url":"https://lyoresearch.com/compounds/exenatide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Exenatide is a synthetic copy of exendin-4, a peptide from Gila-monster saliva, and the drug that opened the GLP-1 class in 2005. It is approved for type 2 diabetes as a twice-daily injection and a weekly one. In the 14,752-person EXSCEL trial it was safe but did not significantly reduce cardiovascular events, unlike the drugs that followed it. A phase 3 trial testing it as a disease-modifying treatment for Parkinson's disease, the use it is most searched for today, found no benefit. It is prescription-only.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"EXSCEL (n=14,752) + DURATION programme + Parkinson's phase 3","regulatory_status":"Approved (Rx)","molecule":{"formula":"C184H282N50O60S","molecular_weight":"4187","cas":"141758-74-9","pubchem_cid":45588096,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, twice daily before meals","half_life":"About 2.4 hours","licensed_regimen":"5 mcg twice daily within 60 minutes before morning and evening meals; may increase to 10 mcg twice daily after 1 month","product":"Byetta","source":{"title":"Byetta prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=53d03c03-ebf7-418d-88a8-533eabd2ee4f"}},"outcomes":[{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"DURATION and AMIGO programmes","evidence":"Approval-grade HbA1c reductions with both formulations; the licensed indication since 2005.","references":[{"citation":"Exenatide (Byetta, Bydureon) product information and the AMIGO / DURATION programmes.","where":"FDA / EMA product information","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/byetta"}]},{"outcome":"Body weight","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"Multiple RCTs","evidence":"Modest, consistent weight loss of a few kilograms in diabetes trials. Not approved for weight management.","references":[{"citation":"Exenatide (Byetta, Bydureon) product information and the AMIGO / DURATION programmes.","where":"FDA / EMA product information","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/byetta"}]},{"outcome":"Major cardiovascular events (type 2 diabetes)","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"1 large RCT (n=14,752, median 3.2 yr)","evidence":"Non-inferior to placebo for safety, but not superior: the 9% relative reduction missed statistical significance. The class benefit shown by liraglutide, semaglutide and dulaglutide was not demonstrated for exenatide.","references":[{"citation":"Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes.","where":"N Engl J Med, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/28910237/"}],"verbatim":{"text":"Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo.","citation":"Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes.","url":"https://pubmed.ncbi.nlm.nih.gov/28910237/"}},{"outcome":"Parkinson's disease progression","grade":"B","grade_meaning":"probable, not settled","effect_size":"not measurable","adverse":false,"human_studies":"1 phase 3 RCT (n=194, 96 wk) — negative; 1 phase 2 positive","evidence":"After a positive 62-person phase 2 in 2017, the 194-person phase 3 found motor scores worsened equally on exenatide and placebo over 96 weeks. The Lancet's editors have since issued an Expression of Concern on the phase 3 paper; the notice does not change the result, but readers should know it exists.","references":[{"citation":"Vijiaratnam N, Girges C, Auld G, et al. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial.","where":"Lancet, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/39919773/"},{"citation":"Athauda D, Maclagan K, Skene SS, et al. Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial.","where":"Lancet, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/28781108/"},{"citation":"The Editors of The Lancet. Expression of Concern: Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42330995/"}],"verbatim":{"text":"At 96 weeks, MDS-UPDRS III OFF-medication scores had increased (worsened) by a mean of 5·7 points (SD 11·2) in the exenatide group, and by 4·5 points (SD 11·4) points in the placebo group (adjusted coefficient for the effect of exenatide 0·92 [95% CI -1·56 to 3·39]; p=0·47).","citation":"Vijiaratnam N, Girges C, Auld G, et al. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/39919773/"}},{"outcome":"Adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"EXSCEL and programme","evidence":"Nausea and other gastrointestinal effects, injection-site nodules with the weekly formulation. Pancreatitis, pancreatic cancer and thyroid carcinoma did not differ from placebo in EXSCEL.","references":[{"citation":"Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes.","where":"N Engl J Med, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/28910237/"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Centrally authorised for type 2 diabetes (Byetta 2006; Bydureon 2011)."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved 2005 (Byetta) and 2012 (Bydureon) for type 2 diabetes."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"MHRA-licensed for type 2 diabetes."},{"region":"Australia","status":"Registered, prescription-only","note":"On the ARTG for type 2 diabetes."},{"region":"Canada","status":"Authorised, prescription-only","note":"Health Canada-authorised for type 2 diabetes."},{"region":"Sport (WADA)","status":"Not prohibited","note":"GLP-1 receptor agonists are not on the Prohibited List."}],"faq":[{"q":"Does exenatide help Parkinson's disease?","a":"The phase 3 trial says no: 194 people over 96 weeks, and motor scores worsened equally on drug and placebo. An earlier 62-person phase 2 had been positive, which is why the larger trial was run. The Lancet has issued an Expression of Concern on the phase 3 paper without stating why."},{"q":"Does exenatide protect the heart like semaglutide?","a":"Not on the evidence. EXSCEL found no significant reduction in cardiovascular events; the 9% relative reduction missed significance. Liraglutide, semaglutide and dulaglutide each showed a benefit in their trials."},{"q":"Is exenatide still used?","a":"It remains approved and available, but has been largely superseded by weekly drugs with larger effects on weight and proven cardiovascular benefit."}],"references":[{"cite":"Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes.","where":"N Engl J Med, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/28910237/","note":"EXSCEL; 14,752 patients; HR 0.91, P=0.06 for superiority."},{"cite":"Vijiaratnam N, Girges C, Auld G, et al. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial.","where":"Lancet, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/39919773/","note":"Exenatide-PD3; 194 participants; 96 weeks; no effect. See ref 5."},{"cite":"Exenatide (Byetta, Bydureon) product information and the AMIGO / DURATION programmes.","where":"FDA / EMA product information","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/byetta","note":"Licensed indications and the glucose and weight data."},{"cite":"Athauda D, Maclagan K, Skene SS, et al. Exenatide once weekly versus placebo in Parkinson's disease: a randomised, double-blind, placebo-controlled trial.","where":"Lancet, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/28781108/","note":"Phase 2; 62 participants; positive on the off-medication motor score — the result the phase 3 was designed to confirm."},{"cite":"The Editors of The Lancet. Expression of Concern: Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK.","where":"Lancet, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42330995/","note":"Notice attached to ref 2. No abstract; the reason is not stated in the notice."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade A on the approval programme and EXSCEL; Parkinson's carries a null phase 3 (grade B, effect none) with the Expression of Concern noted."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"gonadorelin","name":"Gonadorelin (GnRH)","aliases":["gonadotropin-releasing hormone","GnRH","LHRH","Factrel","Lutrelef"],"url":"https://lyoresearch.com/compounds/gonadorelin","class":{"id":"reproductive-hormones","name":"Reproductive and neuroendocrine hormones","url":"https://lyoresearch.com/classes/reproductive-hormones"},"summary":"Gonadorelin is synthetic gonadotropin-releasing hormone, the ten-amino-acid signal the hypothalamus sends to make the pituitary release LH and FSH. Given in pulses by pump it restores fertility in men and women whose own signal is missing; given once it is a licensed test of pituitary function. Neither is what it is mostly sold for today: clinics add it to testosterone replacement to 'keep the testes working', a use that has never been tested in a trial. It is prohibited for male athletes.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"Decades of pulsatile-therapy studies; meta-analysis of 420 men; no trial of the TRT use","regulatory_status":"Licensed (diagnostic / pulsatile); TRT use unstudied","molecule":{"formula":"C55H75N17O13","molecular_weight":"1182.3","cas":"33515-09-2","pubchem_cid":638793,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous or intravenous injection, single diagnostic dose; pulsatile pump for fertility","half_life":"About 4 minutes","licensed_regimen":"100 micrograms SC or IV as a single diagnostic dose","product":"Gonadorelin 100 micrograms powder for solution for injection (UK)","source":{"title":"Gonadorelin 100 micrograms SmPC (UK eMC)","url":"https://www.medicines.org.uk/emc/product/4853/smpc"}},"outcomes":[{"outcome":"LH and FSH release (diagnostic)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Approval-grade","evidence":"A single injection reliably provokes an LH and FSH response, which is the basis of its licence as a pituitary-function test. Not in dispute.","references":[{"citation":"Gonadorelin 100 micrograms powder for solution for injection — Summary of Product Characteristics.","where":"MHRA / emc, UK","url":"https://www.medicines.org.uk/emc/search?q=gonadorelin"}]},{"outcome":"Fertility in hypogonadotropic hypogonadism (pulsatile pump)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"7 comparative studies, 420 men (meta-analysis); many small series","evidence":"In men whose hypothalamus does not produce GnRH, pulsatile gonadorelin by pump induces puberty and sperm production. Against gonadotropin injections it produced larger testes and earlier sperm, but no significant difference in the share who produced sperm, sperm counts or pregnancies; the studies are small and mostly not randomised.","references":[{"citation":"Wei C, Long G, Zhang Y, et al. Spermatogenesis of male patients with congenital hypogonadotropic hypogonadism receiving pulsatile gonadotropin-releasing hormone therapy versus gonadotropin therapy: a systematic review and meta-analysis.","where":"World J Mens Health, 2021;39(4):654–665","url":"https://pubmed.ncbi.nlm.nih.gov/32777865/"}],"verbatim":{"text":"GnRH therapy was related to a larger testicular volume (standardized mean difference=-1.43; p=0.01) and earlier spermatogenesis (WMD=-5.30 months; p=0.004) compared to GT.","citation":"Wei C, Long G, Zhang Y, et al. Spermatogenesis of male patients with congenital hypogonadotropic hypogonadism receiving pulsatile gonadotropin-releasing hormone therapy versus gonadotropin therapy: a systematic review and meta-analysis.","url":"https://pubmed.ncbi.nlm.nih.gov/32777865/"}},{"outcome":"Preserving testicular function on testosterone therapy","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"The use it is most often sold for. A search of the trial literature finds no controlled study of gonadorelin added to testosterone replacement for testicular size, fertility or hormone recovery. The physiological rationale is that intermittent GnRH could keep the pituitary signalling; continuous GnRH does the opposite and shuts it down, which is how the same molecule's analogues treat prostate cancer.","references":[{"citation":"Wei C, Long G, Zhang Y, et al. Spermatogenesis of male patients with congenital hypogonadotropic hypogonadism receiving pulsatile gonadotropin-releasing hormone therapy versus gonadotropin therapy: a systematic review and meta-analysis.","where":"World J Mens Health, 2021;39(4):654–665","url":"https://pubmed.ncbi.nlm.nih.gov/32777865/"},{"citation":"Searches of PubMed and trial registries for gonadorelin added to testosterone replacement therapy.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=gonadorelin+testosterone+replacement+therapy"}]},{"outcome":"Adverse effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"Pulsatile-therapy series","evidence":"Allergic reactions at the infusion site are the characteristic problem of pulsatile therapy; the comparison meta-analysis found fewer oestrogen-related effects (gynaecomastia, acne) than with gonadotropin injections.","references":[{"citation":"Wei C, Long G, Zhang Y, et al. Spermatogenesis of male patients with congenital hypogonadotropic hypogonadism receiving pulsatile gonadotropin-releasing hormone therapy versus gonadotropin therapy: a systematic review and meta-analysis.","where":"World J Mens Health, 2021;39(4):654–665","url":"https://pubmed.ncbi.nlm.nih.gov/32777865/"}]}],"regions":[{"region":"European Union","status":"Authorised in several member states","note":"National authorisations exist as a diagnostic and, in pump form, for hypothalamic infertility; there is no central authorisation. Use alongside testosterone replacement is off-label."},{"region":"United States","status":"Approved products discontinued; compounded","note":"Factrel (diagnostic) and Lutrepulse (pulsatile) were FDA-approved and later withdrawn from the market for commercial reasons. It is now supplied by compounding pharmacies on prescription, which is how TRT clinics use it."},{"region":"United Kingdom","status":"Licensed, prescription-only (diagnostic)","note":"A 100 microgram injection is licensed for assessing pituitary function. Use on testosterone therapy is off-label."},{"region":"Australia","status":"Prescription-only","note":"Schedule 4. LYO did not verify a current ARTG product at review; supply is on prescription or by compounding."},{"region":"Canada","status":"Prescription-only","note":"LYO did not verify a current authorised product at review."},{"region":"Sport (WADA)","status":"Prohibited at all times (males)","note":"Gonadorelin is named on the Prohibited List among gonadotrophin-releasing factors, prohibited in males in and out of competition."}],"faq":[{"q":"Does gonadorelin keep your testicles from shrinking on TRT?","a":"There is no trial. The idea is that pulses of GnRH keep the pituitary signalling to the testes while testosterone suppresses it; the same molecule given continuously shuts the axis down. Whether a few injections a week does the first or the second has not been studied. hCG, which acts directly on the testes, is the better-documented option for that purpose."},{"q":"Is gonadorelin the same as hCG?","a":"No. Gonadorelin acts on the pituitary and needs pulsing; hCG acts directly on the testes as an LH substitute. They sit at different points in the same axis."},{"q":"Is gonadorelin legal?","a":"It is a licensed medicine in several countries for diagnosis and fertility, compounded on prescription in the US, and prohibited in sport for men. Use alongside testosterone therapy is off-label everywhere."}],"references":[{"cite":"Wei C, Long G, Zhang Y, et al. Spermatogenesis of male patients with congenital hypogonadotropic hypogonadism receiving pulsatile gonadotropin-releasing hormone therapy versus gonadotropin therapy: a systematic review and meta-analysis.","where":"World J Mens Health, 2021;39(4):654–665","url":"https://pubmed.ncbi.nlm.nih.gov/32777865/","note":"7 studies, 420 men; mostly non-randomised."},{"cite":"Searches of PubMed and trial registries for gonadorelin added to testosterone replacement therapy.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=gonadorelin+testosterone+replacement+therapy","note":"No controlled trial of the TRT use identified."},{"cite":"Gonadorelin 100 micrograms powder for solution for injection — Summary of Product Characteristics.","where":"MHRA / emc, UK","url":"https://www.medicines.org.uk/emc/search?q=gonadorelin","note":"Licensed diagnostic use."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. A for the diagnostic response, B for pulsatile fertility therapy, D for the TRT use on absence of any trial."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"afamelanotide","name":"Afamelanotide (Melanotan I)","aliases":["Melanotan I","Melanotan-1","Scenesse","CUV1647","NDP-MSH"],"url":"https://lyoresearch.com/compounds/afamelanotide","class":{"id":"melanocortins","name":"Melanocortin agonists","url":"https://lyoresearch.com/classes/melanocortins"},"summary":"Afamelanotide is a linear analogue of the pigment hormone α-MSH, developed in the 1980s as the first 'Melanotan'. It is an approved medicine — as a subcutaneous implant replaced every two months — for erythropoietic protoporphyria, a genetic disorder in which sunlight causes severe pain within minutes. In two randomised trials it roughly doubled the hours patients could spend in direct sun without pain. The same molecule is sold illegally as a tanning injection; for that use there is no approval and no controlled evidence of safety.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"2 phase 3 RCTs (n=168) + long-term registry data","regulatory_status":"Approved (Rx) — erythropoietic protoporphyria","molecule":{"formula":"C78H111N21O19","molecular_weight":"1646.8","cas":"75921-69-6","pubchem_cid":16197727,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous implant, every 2 months","half_life":"About 15 hours (apparent, from implant)","licensed_regimen":"Single 16 mg implant inserted subcutaneously every 2 months","product":"Scenesse","source":{"title":"Scenesse prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=94f53286-11dd-7fbb-e053-2a95a90a7c48"}},"outcomes":[{"outcome":"Pain-free sun exposure in erythropoietic protoporphyria","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"2 phase 3 RCTs (EU n=74, US n=94)","evidence":"In both trials patients on afamelanotide implants spent significantly longer in direct sunlight without pain; the EU trial also counted fewer phototoxic reactions. Quality of life improved in both.","references":[{"citation":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","where":"N Engl J Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/"}],"verbatim":{"text":"In the U.S. study, the duration of pain-free time after 6 months was longer in the afamelanotide group (median, 69.4 hours, vs. 40.8 hours in the placebo group; P=0.04).","citation":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/"}},{"outcome":"Skin pigmentation (tanning)","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"Early trials + the phase 3 programme","evidence":"It darkens skin reliably — that is its mechanism, and hyperpigmentation is the expected effect in every trial. What has never been studied is the safety of using it for cosmetic tanning in healthy people, and no regulator has approved that use.","references":[{"citation":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","where":"N Engl J Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/"}]},{"outcome":"Vitiligo repigmentation","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Small RCTs with phototherapy","evidence":"Small trials combining the implant with narrowband UVB reported faster repigmentation than phototherapy alone. Not an approved indication.","references":[{"citation":"Afamelanotide with narrowband UV-B phototherapy for vitiligo — randomised trials.","where":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=afamelanotide+vitiligo+randomized+narrowband"}]},{"outcome":"Adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":true,"human_studies":"Phase 3 + registry","evidence":"Nausea, headache and implant-site reactions; darkening of skin and moles, which requires skin monitoring on treatment. Serious events in the trials were not judged drug-related.","references":[{"citation":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","where":"N Engl J Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/"}],"verbatim":{"text":"Adverse events were mostly mild; serious adverse events were not thought to be related to the study drug.","citation":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/"}}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Centrally authorised (Scenesse) in 2014 under exceptional circumstances for erythropoietic protoporphyria. Tanning use is not authorised; injectable 'Melanotan' products are illegal."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved October 2019 for erythropoietic protoporphyria, implant only."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Licensed for erythropoietic protoporphyria. The MHRA has repeatedly warned against injectable tanning products."},{"region":"Australia","status":"Registered, prescription-only","note":"On the ARTG for erythropoietic protoporphyria; the developer is Australian."},{"region":"Canada","status":"Not authorised","note":"LYO found no Health Canada authorisation at review."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the Prohibited List."}],"faq":[{"q":"Is Melanotan I the same as Melanotan II?","a":"No. Melanotan I is linear and selective for the pigment receptor; Melanotan II is cyclic and hits several melanocortin receptors, which is why it also causes erections and nausea. Melanotan I became an approved medicine; Melanotan II did not."},{"q":"Can you get afamelanotide for tanning?","a":"Not lawfully. It is approved only for erythropoietic protoporphyria, as an implant placed by a clinician. The injectable 'Melanotan I' sold online is an unlicensed product of unknown content."},{"q":"Does it cause skin cancer?","a":"Unknown; it is the main open safety question. It darkens moles, so treated patients have regular skin checks. Registry data over years of licensed use have not shown an excess so far."}],"references":[{"cite":"Langendonk JG, Balwani M, Anderson KE, et al. Afamelanotide for erythropoietic protoporphyria.","where":"N Engl J Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/26132941/","note":"Two phase 3 trials; EU n=74, US n=94."},{"cite":"Scenesse (afamelanotide) — European public assessment report.","where":"EMA, 2014 onward","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/scenesse","note":"Licensed indication and conditions."},{"cite":"Afamelanotide with narrowband UV-B phototherapy for vitiligo — randomised trials.","where":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=afamelanotide+vitiligo+randomized+narrowband","note":"Small trials; not an approved indication."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade A for erythropoietic protoporphyria on two phase 3 RCTs."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"setmelanotide","name":"Setmelanotide","aliases":["Imcivree","RM-493","BIM-22493","MC4R agonist"],"url":"https://lyoresearch.com/compounds/setmelanotide","class":{"id":"melanocortins","name":"Melanocortin agonists","url":"https://lyoresearch.com/classes/melanocortins"},"summary":"Setmelanotide is a cyclic analogue of α-MSH that activates the MC4 receptor, the brain's main satiety switch. In people whose obesity is caused by rare mutations upstream of that receptor — POMC, PCSK1 or LEPR deficiency, or Bardet-Biedl syndrome — it restores the signal: 80% of POMC-deficient and 45% of LEPR-deficient patients lost at least a tenth of their body weight in a year, with hunger scores falling by a quarter to a half. Those trials had ten and eleven participants. In obesity that follows damage to the hypothalamus, a 120-person randomised trial found BMI fell 16.5% against a 3.3% rise on placebo; Canada approved that use in September 2026. It has no role in common obesity.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"Single-arm phase 3 trials (n=10, n=11) with placebo-withdrawal; BBS trial (n=38); acquired hypothalamic obesity phase 3 RCT (n=120)","regulatory_status":"Approved (Rx) — rare genetic obesity; hypothalamic obesity in Canada","molecule":{"formula":"C49H68N18O9S2","molecular_weight":"1117.3","cas":"920014-72-8","pubchem_cid":11993702,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, once daily","half_life":"About 11 hours","licensed_regimen":"Adults and children ≥12 years: 2 mg daily for 2 weeks, then 3 mg daily; 6 to <12 years: 1 mg daily for 2 weeks, then 3 mg daily","product":"Imcivree","source":{"title":"Imcivree prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=70c3ccf7-4df0-4c75-ba07-fede9970c8d9"}},"outcomes":[{"outcome":"Weight loss in POMC / LEPR deficiency obesity","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"2 single-arm phase 3 trials (n=10, n=11) with 8-wk placebo withdrawal","evidence":"Eight of ten POMC-deficient and five of eleven LEPR-deficient participants lost at least 10% of body weight at about a year, with weight regained during the blinded placebo-withdrawal weeks. Large effects; tiny trials.","references":[{"citation":"Clément K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials.","where":"Lancet Diabetes Endocrinol, 2020","url":"https://pubmed.ncbi.nlm.nih.gov/33137293/"}],"verbatim":{"text":"Eight (80%) participants in the POMC trial and five (45%) participants in the LEPR trial achieved at least 10% weight loss at approximately 1 year.","citation":"Clément K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials.","url":"https://pubmed.ncbi.nlm.nih.gov/33137293/"}},{"outcome":"Hunger in POMC / LEPR deficiency","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"Same trials","evidence":"The 'most hunger' score fell by 27% and 44% — the mechanism working as designed in people whose hunger signal is broken.","references":[{"citation":"Clément K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials.","where":"Lancet Diabetes Endocrinol, 2020","url":"https://pubmed.ncbi.nlm.nih.gov/33137293/"}],"verbatim":{"text":"The mean percentage change in the most hunger score was -27·1% (n=7; 90% CI -40·6 to -15·0; p=0·0005) in the POMC trial and -43·7% (n=7; -54·8 to -29·1; p<0·0001) in the LEPR trial.","citation":"Clément K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials.","url":"https://pubmed.ncbi.nlm.nih.gov/33137293/"}},{"outcome":"Weight loss in Bardet-Biedl syndrome","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 with 14-wk placebo-controlled period (n=38)","evidence":"The basis of the 2022 approval extension; the only setmelanotide trial with a randomised placebo period.","references":[{"citation":"Haqq AM, et al. Efficacy and safety of setmelanotide in Bardet-Biedl syndrome: a phase 3 randomised, placebo-controlled trial.","where":"Lancet Diabetes Endocrinol, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Haqq+setmelanotide+Bardet-Biedl+phase+3+2022"}]},{"outcome":"Weight loss in acquired hypothalamic obesity","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 phase 3 RCT (TRANSCEND, n=120, 52 wk)","evidence":"TRANSCEND, published in the New England Journal of Medicine in July 2026: 120 people aged 4 to 66 whose obesity followed a hypothalamic tumour, lesion or injury were randomised 2:1 to setmelanotide or placebo. BMI fell 16.5% on setmelanotide and rose 3.3% on placebo at 52 weeks, and hunger scores fell further on the drug. Serious adverse events were reported in 28% against 8%. One randomised trial, so B. Health Canada approved this use on 22 September 2026.","references":[{"citation":"Miller JL, et al. Setmelanotide for the treatment of acquired hypothalamic obesity (TRANSCEND).","where":"N Engl J Med, 2026;395(2):138–150","url":"https://pubmed.ncbi.nlm.nih.gov/42418774/"},{"citation":"Rhythm Pharmaceuticals. Health Canada approval of Imcivree (setmelanotide) for weight management in adult and paediatric patients 4 years of age and older with acquired hypothalamic obesity.","where":"Press release, 22 Sep 2026","url":"https://ir.rhythmtx.com/news-releases/news-release-details/rhythm-pharmaceuticals-announces-health-canada-approval-0"}],"verbatim":{"text":"The least-squares mean (LSM) change in BMI at 52 weeks was -16.5% (95% confidence interval [CI], -19.3 to -13.8) with setmelanotide and 3.3% (95% CI, -0.6 to 7.2) with placebo (P<0.001), and the LSM change in the weekly average of maximal daily hunger scores was -2.73 (95% CI, -3.28 to -2.18) in the setmelanotide group and -1.45 (95% CI, -2.23 to -0.67) in the placebo group (P = 0.009).","citation":"Miller JL, et al. Setmelanotide for the treatment of acquired hypothalamic obesity (TRANSCEND).","url":"https://pubmed.ncbi.nlm.nih.gov/42418774/"}},{"outcome":"Common (polygenic) obesity","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"No approved use; early trials only","evidence":"Not developed for obesity without a monogenic cause. Early-phase work in general obesity showed effects too small to pursue; no controlled trial supports the use and no regulator has approved it.","references":[{"citation":"Imcivree (setmelanotide) — European public assessment report.","where":"EMA, 2021 onward","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/imcivree"}]},{"outcome":"Adverse effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":true,"human_studies":"Same trials","evidence":"Injection-site reactions and skin darkening in every participant, nausea and vomiting in a third to a half; hyperpigmentation is the MC1-receptor effect the drug cannot avoid.","references":[{"citation":"Clément K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials.","where":"Lancet Diabetes Endocrinol, 2020","url":"https://pubmed.ncbi.nlm.nih.gov/33137293/"}],"verbatim":{"text":"The most common adverse events were injection site reaction and hyperpigmentation, which were reported in all ten participants in the POMC trial; nausea was reported in five participants and vomiting in three participants.","citation":"Clément K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials.","url":"https://pubmed.ncbi.nlm.nih.gov/33137293/"}}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Centrally authorised (Imcivree) 2021 for POMC, PCSK1 or LEPR deficiency obesity; 2022 for Bardet-Biedl syndrome. Genetic confirmation required."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved November 2020 for POMC, PCSK1 or LEPR deficiency; June 2022 for Bardet-Biedl syndrome."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Licensed for the same genetic indications."},{"region":"Australia","status":"Prescription-only","note":"LYO did not verify an ARTG entry at review; no approval for common obesity anywhere."},{"region":"Canada","status":"Approved, prescription-only","note":"According to the manufacturer, Health Canada approved Imcivree in 2023 for obesity due to Bardet-Biedl syndrome or POMC, PCSK1 or LEPR deficiency (age 6 and over), and on 22 September 2026 for acquired hypothalamic obesity (age 4 and over)."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the Prohibited List."}],"faq":[{"q":"Can setmelanotide be used for ordinary obesity?","a":"No. It restores a signal that is broken by specific mutations. In people without those mutations the signal is not broken, early studies found little effect, and no regulator has approved it for that use."},{"q":"Why is an approved drug graded B?","a":"Because the pivotal trials had ten and eleven participants and no parallel placebo group — the design regulators accept for ultra-rare diseases. The effect is large and the grade reflects certainty, not size."},{"q":"How is it different from Melanotan II or PT-141?","a":"All three are α-MSH analogues, but setmelanotide is selective for MC4R, the appetite receptor, and is approved for a genetic disease. PT-141 targets sexual desire; Melanotan II is a non-selective grey-market product. The skin darkening is shared."}],"references":[{"cite":"Clément K, van den Akker E, Argente J, et al. Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials.","where":"Lancet Diabetes Endocrinol, 2020","url":"https://pubmed.ncbi.nlm.nih.gov/33137293/","note":"POMC n=10, LEPR n=11."},{"cite":"Imcivree (setmelanotide) — European public assessment report.","where":"EMA, 2021 onward","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/imcivree","note":"Licensed indications; genetic confirmation required."},{"cite":"Haqq AM, et al. Efficacy and safety of setmelanotide in Bardet-Biedl syndrome: a phase 3 randomised, placebo-controlled trial.","where":"Lancet Diabetes Endocrinol, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Haqq+setmelanotide+Bardet-Biedl+phase+3+2022","note":"n=38; 14-week placebo-controlled period."},{"cite":"Miller JL, et al. Setmelanotide for the treatment of acquired hypothalamic obesity (TRANSCEND).","where":"N Engl J Med, 2026;395(2):138–150","url":"https://pubmed.ncbi.nlm.nih.gov/42418774/","note":"120 randomised 2:1, 52 weeks; BMI −16.5% vs +3.3%. NCT05774756."},{"cite":"Rhythm Pharmaceuticals. Health Canada approval of Imcivree (setmelanotide) for weight management in adult and paediatric patients 4 years of age and older with acquired hypothalamic obesity.","where":"Press release, 22 Sep 2026","url":"https://ir.rhythmtx.com/news-releases/news-release-details/rhythm-pharmaceuticals-announces-health-canada-approval-0","note":"Also states the 2023 Canadian approval for Bardet-Biedl syndrome and POMC, PCSK1 or LEPR deficiency. Company source."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"New row for acquired hypothalamic obesity from the published TRANSCEND trial (N Engl J Med, July 2026; n=120), graded B. Canada row updated: approved, including the acquired hypothalamic obesity indication of 22 Sep 2026. Other grades unchanged."},{"date":"2026-09-10","note":"Initial publication. Grade B for the genetic indications on tiny single-arm trials; D for common obesity."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"follistatin-344","name":"Follistatin 344","aliases":["FS344","follistatin","FST-344","myostatin inhibitor"],"url":"https://lyoresearch.com/compounds/follistatin-344","class":{"id":"growth-hormone-and-igf","name":"Growth hormone, IGF-1 and growth factors","url":"https://lyoresearch.com/classes/growth-hormone-and-igf"},"summary":"Follistatin is a natural protein that binds and blocks myostatin, the signal that limits muscle growth; animals engineered to overexpress it become dramatically muscular. 'Follistatin 344' is the full-length form, sold as a lyophilised injectable for muscle. No human trial has ever tested injecting it. The only clinical data is a 2015 gene-therapy study in six men with Becker muscular dystrophy, in which a virus carrying the follistatin gene was injected into the thigh muscles — some walked further, some did not, and it is not the product being sold. It is prohibited in sport.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 for the injected protein; 1 gene-therapy trial (n=6)","regulatory_status":"Not approved; research reagent","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"A 344-residue glycoprotein — no small-molecule record"},"pharmacokinetics":{"basis":"none","route":"Injected as sold; no human study of the peptide","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Muscle growth / strength (injected protein)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"No human study of any kind has given follistatin protein by injection. The grey-market product has no clinical file, and a 344-residue glycoprotein injected subcutaneously would be expected to be cleared quickly and to bind targets far beyond muscle.","references":[{"citation":"Searches of PubMed and trial registries for injected follistatin in humans.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=follistatin+injection+human+trial+muscle"}]},{"outcome":"Muscle function in Becker muscular dystrophy (gene therapy)","grade":"D","grade_meaning":"no human evidence","effect_size":"small","adverse":false,"human_studies":"1 open-label phase 1/2a (n=6)","evidence":"A follistatin gene delivered by AAV into the quadriceps of six patients: four walked further on the six-minute test, two did not change, with no control group. Encouraging as proof of principle; not evidence for the injected protein, and not evidence in healthy people.","references":[{"citation":"Mendell JR, Sahenk Z, Malik V, et al. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy.","where":"Mol Ther, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/25322757/"}],"verbatim":{"text":"AAV1.CMV.FS344 was delivered to six BMD patients by direct bilateral intramuscular quadriceps injections.","citation":"Mendell JR, Sahenk Z, Malik V, et al. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy.","url":"https://pubmed.ncbi.nlm.nih.gov/25322757/"}},{"outcome":"Fat loss","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Claimed on the basis of myostatin-knockout animals; no human data.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None for the protein","evidence":"Follistatin also neutralises activin, which regulates reproduction, inflammation and the pituitary. Systemic blockade in humans has never been characterised. The gene-therapy trial reported no adverse effects in six people over a limited follow-up — in muscle-restricted delivery.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation anywhere. Supplying it for human use is an offence under national medicines law."},{"region":"United States","status":"Not approved","note":"Sold as a research reagent 'not for human use'; no clinical programme for the protein."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence; supply for human use is an offence."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Myostatin inhibitors are prohibited under the S4 class (agents preventing activin receptor IIB activation), in and out of competition."}],"faq":[{"q":"Does follistatin 344 build muscle?","a":"In animals engineered to make more of it, dramatically. In humans, no trial has tested injecting it, so the honest answer is unknown — and the six-patient gene-therapy study people cite used a virus to make muscle produce it locally, which is a different intervention."},{"q":"Is the gene-therapy trial evidence for the injection?","a":"No. Local, continuous production inside the muscle from a delivered gene is not the same as a protein injected under the skin, which is cleared quickly and acts everywhere. The trial also had six patients and no control group."},{"q":"Is follistatin safe?","a":"Unknown. It blocks activin as well as myostatin, and activin does many things — including in reproduction. No one has measured what happens when it is blocked systemically in people."}],"references":[{"cite":"Mendell JR, Sahenk Z, Malik V, et al. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy.","where":"Mol Ther, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/25322757/","note":"Six patients; AAV1.CMV.FS344 injected into the quadriceps; no control group."},{"cite":"Searches of PubMed and trial registries for injected follistatin in humans.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=follistatin+injection+human+trial+muscle","note":"No human trial of the injected protein identified."},{"cite":"World Anti-Doping Agency. The Prohibited List — S4: hormone and metabolic modulators.","where":"WADA, current list","url":"https://www.wada-ama.org/en/prohibited-list","note":"Myostatin inhibitors / agents preventing activin receptor IIB activation."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade D on absence of any human trial of the injected protein; the gene-therapy study is described and separated."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"noopept","name":"Noopept (omberacetam)","aliases":["omberacetam","GVS-111","N-phenylacetyl-L-prolylglycine ethyl ester","Noopept"],"url":"https://lyoresearch.com/compounds/noopept","class":{"id":"nootropic-peptides","name":"Nootropic and sleep peptides","url":"https://lyoresearch.com/classes/nootropic-peptides"},"summary":"Noopept is a synthetic molecule built from the dipeptide proline-glycine, developed at the Zakusov Institute in Moscow and registered in Russia as a nootropic for mild cognitive impairment after brain injury or stroke. Outside Russia it is not approved anywhere. The human evidence is a single Russian comparison against piracetam in patients with vascular or traumatic cognitive impairment; its English translation carries no abstract in PubMed, and no independent group has replicated it. The claims made for it in healthy people — focus, memory, learning — have never been tested in a controlled trial.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"1 Russian comparative trial vs piracetam (2008); no independent replication","regulatory_status":"Not approved (outside Russia)","molecule":{"formula":"C17H22N2O4","molecular_weight":"318.4","cas":"157115-85-0","pubchem_cid":180496,"note":null},"pharmacokinetics":{"basis":"animal","route":"Oral","half_life":"No human pharmacokinetic data; rat studies only","licensed_regimen":null,"product":null,"source":{"title":"Boiko SS, et al. Pharmacokinetics of new nootropic acylprolyldipeptide and its penetration across the blood-brain barrier after oral administration. Bull Exp Biol Med 2000","url":"https://pubmed.ncbi.nlm.nih.gov/10977920/"}},"outcomes":[{"outcome":"Cognitive impairment after brain injury or stroke","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 Russian comparative trial (vs piracetam)","evidence":"The basis of the Russian registration. Published in Russian in 2008 and in translation in 2009; the indexed record has no abstract, so the size, blinding and outcome measures cannot be assessed from the international literature. Not replicated.","references":[{"citation":"Neznamov GG, Teleshova ES. Comparative studies of Noopept and piracetam in the treatment of patients with mild cognitive disorders in organic brain diseases of vascular and traumatic origin.","where":"Neurosci Behav Physiol, 2009","url":"https://pubmed.ncbi.nlm.nih.gov/19234797/"},{"citation":"Neznamov GG, Teleshova ES. [A comparative study of noopept and piracetam in the treatment of mild and moderate cognitive impairment in patients with organic brain diseases of vascular and traumatic origin].","where":"Zh Nevrol Psikhiatr Im S S Korsakova, 2008 (Russian)","url":"https://pubmed.ncbi.nlm.nih.gov/18697252/"}]},{"outcome":"Cognition in healthy people","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"The nootropic use it is sold for. No controlled human study.","references":[{"citation":"Searches of PubMed and trial registries for omberacetam / Noopept in healthy volunteers.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=noopept+OR+omberacetam+healthy+volunteers+randomized"}]},{"outcome":"Anxiety","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None controlled","evidence":"Anxiolytic effects are reported in the Russian literature and in rodents; no controlled human trial.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"No systematic international data","evidence":"Reported as well tolerated in Russian use. No pharmacovigilance dataset outside Russia; no data on long-term use.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation in any member state. Sold online as a 'supplement', which it is not."},{"region":"United States","status":"Not approved","note":"Not an approved drug and not a lawful dietary-supplement ingredient."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence; supply for human use is an offence."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Not on the list","note":"Not named on the Prohibited List."}],"faq":[{"q":"Is Noopept approved anywhere?","a":"In Russia, since 2007, for cognitive impairment after brain injury or stroke. Not in the EU, US, UK, Australia or Canada."},{"q":"Does Noopept improve memory or focus?","a":"There is no controlled trial in healthy people. The one clinical study is in patients with brain injury or stroke, published in Russian, and cannot be evaluated from the indexed literature."},{"q":"Is Noopept a peptide?","a":"It is built from a dipeptide and often called a 'peptide nootropic', but it is a small synthetic ester. Its proposed active metabolite, cycloprolylglycine, is a true dipeptide."}],"references":[{"cite":"Neznamov GG, Teleshova ES. Comparative studies of Noopept and piracetam in the treatment of patients with mild cognitive disorders in organic brain diseases of vascular and traumatic origin.","where":"Neurosci Behav Physiol, 2009","url":"https://pubmed.ncbi.nlm.nih.gov/19234797/","note":"Translation of the 2008 Russian paper. No abstract available in PubMed."},{"cite":"Neznamov GG, Teleshova ES. [A comparative study of noopept and piracetam in the treatment of mild and moderate cognitive impairment in patients with organic brain diseases of vascular and traumatic origin].","where":"Zh Nevrol Psikhiatr Im S S Korsakova, 2008 (Russian)","url":"https://pubmed.ncbi.nlm.nih.gov/18697252/","note":"Original Russian-language report."},{"cite":"Searches of PubMed and trial registries for omberacetam / Noopept in healthy volunteers.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=noopept+OR+omberacetam+healthy+volunteers+randomized","note":"No controlled trial identified."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade D throughout: one unreplicated Russian trial without an indexed abstract."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"cerebrolysin","name":"Cerebrolysin","aliases":["Cerebrolysin","FPF-1070","porcine brain peptide preparation"],"url":"https://lyoresearch.com/compounds/cerebrolysin","class":{"id":"nootropic-peptides","name":"Nootropic and sleep peptides","url":"https://lyoresearch.com/classes/nootropic-peptides"},"summary":"Cerebrolysin is a mixture of short peptides and amino acids extracted from pig brain, made in Austria and given as a course of daily intravenous infusions for stroke, dementia and brain injury in Russia, China, Eastern Europe and Asia. It is not approved in the United States, the United Kingdom or EU-wide. The Cochrane review of seven stroke trials found no effect on death and a doubling of non-fatal serious adverse events; the Cochrane review of six vascular-dementia trials found a small cognitive benefit on very low-quality evidence that may be too small to matter.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"7 RCTs in stroke (n=1,773); 6 RCTs in vascular dementia (n=597); many small trials","regulatory_status":"Approved in Austria, Russia, China and others; not US/UK/EU-wide","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"An undefined mixture of porcine brain peptides — no molecular identity"},"pharmacokinetics":{"basis":"none","route":"Intravenous or intramuscular as used clinically","half_life":"No pharmacokinetic data — an undefined peptide mixture has no single half-life","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Survival after acute ischaemic stroke","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"Cochrane review: 6 RCTs, 1,689 participants","evidence":"Moderate-certainty evidence of no effect on death. None of the trials reported the outcome that matters most — death or dependence — at all.","references":[{"citation":"Ziganshina LE, Abakumova T, Nurkhametova D, Ivanchenko K. Cerebrolysin for acute ischaemic stroke.","where":"Cochrane Database Syst Rev, 2023;10:CD007026","url":"https://pubmed.ncbi.nlm.nih.gov/37818733/"}],"verbatim":{"text":"All-cause death: Cerebrolysin or Cortexin probably result in little to no difference in all-cause death (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.65 to 1.41; 6 trials, 1689 participants; moderate-certainty evidence).","citation":"Ziganshina LE, Abakumova T, Nurkhametova D, Ivanchenko K. Cerebrolysin for acute ischaemic stroke.","url":"https://pubmed.ncbi.nlm.nih.gov/37818733/"}},{"outcome":"Cognition in vascular dementia","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Cochrane review: 6 RCTs, 597 participants","evidence":"A small pooled benefit on cognitive scores, from trials the reviewers rated at high risk of bias and very low quality, with no new trials in a decade. Their own conclusion: if there are benefits, they may be too small to be clinically meaningful.","references":[{"citation":"Cui S, Chen N, Yang M, et al. Cerebrolysin for vascular dementia.","where":"Cochrane Database Syst Rev, 2019;11:CD008900","url":"https://pubmed.ncbi.nlm.nih.gov/31710397/"}],"verbatim":{"text":"Combining the MMSE and ADAS-cog+ data (three studies, 420 people), there was a beneficial effect of Cerebrolysin (SMD 0.36, 95% CI 0.13 to 0.58; very low-quality evidence).","citation":"Cui S, Chen N, Yang M, et al. Cerebrolysin for vascular dementia.","url":"https://pubmed.ncbi.nlm.nih.gov/31710397/"}},{"outcome":"Alzheimer's disease","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Several small RCTs","evidence":"Small trials report modest short-term improvements on cognitive scales; no large or long trial, no regulatory approval in a major market for this use.","references":[{"citation":"Cerebrolysin randomised trials in Alzheimer's disease and traumatic brain injury.","where":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=cerebrolysin+randomized+controlled+trial"}]},{"outcome":"Traumatic brain injury recovery","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Small RCTs and cohort studies","evidence":"A mix of small randomised and observational studies from the countries where it is used; not independently confirmed at scale.","references":[{"citation":"Cerebrolysin randomised trials in Alzheimer's disease and traumatic brain injury.","where":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=cerebrolysin+randomized+controlled+trial"}]},{"outcome":"Serious adverse events (stroke)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"Cochrane review: 3 RCTs, 1,335 participants","evidence":"Non-fatal serious adverse events were more than twice as common on Cerebrolysin, and more so at the higher cumulative dose — moderate-certainty evidence.","references":[{"citation":"Ziganshina LE, Abakumova T, Nurkhametova D, Ivanchenko K. Cerebrolysin for acute ischaemic stroke.","where":"Cochrane Database Syst Rev, 2023;10:CD007026","url":"https://pubmed.ncbi.nlm.nih.gov/37818733/"}],"verbatim":{"text":"This comprised fatal SAEs (RR 0.90, 95% CI 0.59 to 1.38; 3 trials, 1335 participants; moderate-certainty evidence) and an increase in the total number of people with non-fatal SAEs (RR 2.39, 95% CI 1.10 to 5.23; 3 trials, 1335 participants; moderate-certainty evidence).","citation":"Ziganshina LE, Abakumova T, Nurkhametova D, Ivanchenko K. Cerebrolysin for acute ischaemic stroke.","url":"https://pubmed.ncbi.nlm.nih.gov/37818733/"}}],"regions":[{"region":"European Union","status":"Authorised nationally in Austria and some member states","note":"No central (EU-wide) authorisation. Where authorised, prescription-only and given by infusion."},{"region":"United States","status":"Not approved","note":"Not FDA-approved; imported products are unapproved drugs."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence."},{"region":"Australia","status":"Not registered","note":"Not on the ARTG."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Not on the list","note":"Not named on the Prohibited List."}],"faq":[{"q":"Does Cerebrolysin work for stroke?","a":"The Cochrane review of seven randomised trials found no effect on death and no reported data on dependence, with more serious adverse events on treatment. That is the best available summary, and it is negative."},{"q":"Does Cerebrolysin help dementia?","a":"A small pooled benefit on cognitive scores in vascular dementia, from trials of very low quality; the reviewers judged any benefit might be too small to be meaningful. No large, independent trial has been done in over a decade."},{"q":"Why is it approved in some countries and not others?","a":"It predates modern licensing standards in the countries where it is established, and the trial evidence has not met the bar of the FDA, MHRA or EMA. National approvals in Austria and elsewhere remain."}],"references":[{"cite":"Ziganshina LE, Abakumova T, Nurkhametova D, Ivanchenko K. Cerebrolysin for acute ischaemic stroke.","where":"Cochrane Database Syst Rev, 2023;10:CD007026","url":"https://pubmed.ncbi.nlm.nih.gov/37818733/","note":"Seven RCTs, 1,773 participants."},{"cite":"Cui S, Chen N, Yang M, et al. Cerebrolysin for vascular dementia.","where":"Cochrane Database Syst Rev, 2019;11:CD008900","url":"https://pubmed.ncbi.nlm.nih.gov/31710397/","note":"Six RCTs, 597 participants; very low-quality evidence."},{"cite":"Cerebrolysin randomised trials in Alzheimer's disease and traumatic brain injury.","where":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=cerebrolysin+randomized+controlled+trial","note":"Small trials, largely from countries where the product is established."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Stroke survival graded A (no effect) on moderate-certainty Cochrane evidence; dementia C."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"teriparatide","name":"Teriparatide","aliases":["Forteo","Forsteo","PTH(1-34)","parathyroid hormone 1-34","recombinant human parathyroid hormone"],"url":"https://lyoresearch.com/compounds/teriparatide","class":{"id":"endocrine-medicines","name":"Bone and endocrine peptide medicines","url":"https://lyoresearch.com/classes/endocrine-medicines"},"summary":"Teriparatide is the first 34 amino acids of human parathyroid hormone, given as a daily injection for severe osteoporosis. Continuous parathyroid hormone strips bone; a brief daily pulse builds it — which is why the drug works and the hormone's excess does not. In the 1,637-woman trial behind its approval, new spinal fractures fell from 14% to 5% over about 21 months and non-spinal fragility fractures roughly halved. It is a prescription medicine, approved everywhere, with a long safety record; the original two-year lifetime limit was lifted by the FDA in 2020.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"Fracture Prevention Trial (n=1,637) + head-to-head VERO trial","regulatory_status":"Approved (Rx)","molecule":{"formula":"C181H291N55O51S2","molecular_weight":"4118","cas":"52232-67-4","pubchem_cid":16133850,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, once daily","half_life":"About 1 hour","licensed_regimen":"20 mcg subcutaneously once daily","product":"Forteo","source":{"title":"Forteo prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aae667c5-381f-4f92-93df-2ed6158d07b0"}},"outcomes":[{"outcome":"Vertebral fracture risk (postmenopausal osteoporosis)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"1 large RCT (n=1,637, median 21 mo)","evidence":"New spinal fractures in 14% on placebo against 5% and 4% on the two teriparatide doses — a relative risk of about 0.35. The trial was stopped early, on a rat osteosarcoma signal rather than efficacy, and still showed this.","references":[{"citation":"Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.","where":"N Engl J Med, 2001","url":"https://pubmed.ncbi.nlm.nih.gov/11346808/"}],"verbatim":{"text":"New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-microg and 40-microg parathyroid hormone groups; the respective relative risks of fracture in the 20-microg and 40-microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50).","citation":"Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.","url":"https://pubmed.ncbi.nlm.nih.gov/11346808/"}},{"outcome":"Non-vertebral fracture risk","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Same RCT","evidence":"Non-spinal fragility fractures fell from 6% to 3% — relative risk about 0.47. Hip fractures specifically were too few to analyse in this trial.","references":[{"citation":"Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.","where":"N Engl J Med, 2001","url":"https://pubmed.ncbi.nlm.nih.gov/11346808/"}]},{"outcome":"Bone mineral density","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Same RCT + many","evidence":"Spine density rose 9–13 percentage points more than placebo, femoral neck 3–6 — the largest gains of any osteoporosis drug — with a small loss at the wrist shaft.","references":[{"citation":"Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.","where":"N Engl J Med, 2001","url":"https://pubmed.ncbi.nlm.nih.gov/11346808/"}],"verbatim":{"text":"As compared with placebo, the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points.","citation":"Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.","url":"https://pubmed.ncbi.nlm.nih.gov/11346808/"}},{"outcome":"Versus risedronate (head-to-head)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"VERO RCT (n=1,360, 24 mo)","evidence":"In a direct comparison against a standard bisphosphonate in women with severe osteoporosis, teriparatide produced fewer new vertebral fractures. The result that moved it from second-line to first-line for the highest-risk patients in many guidelines.","references":[{"citation":"Kendler DL, Marin F, Zerbini CAF, et al. Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.","where":"Lancet, 2018","url":"https://pubmed.ncbi.nlm.nih.gov/?term=VERO+teriparatide+risedronate+Kendler+Lancet+2018"}]},{"outcome":"Adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":true,"human_studies":"Approval trial + 20 years of surveillance","evidence":"Nausea, headache, leg cramps, transient high calcium. The rat osteosarcoma finding that limited use to two years was never seen at excess in people; the FDA removed the limit and the boxed warning in 2020.","references":[{"citation":"Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.","where":"N Engl J Med, 2001","url":"https://pubmed.ncbi.nlm.nih.gov/11346808/"},{"citation":"Teriparatide (Forteo) prescribing information — 2020 label update removing the two-year limit and boxed warning.","where":"FDA","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}],"verbatim":{"text":"Parathyroid hormone had only minor side effects (occasional nausea and headache).","citation":"Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.","url":"https://pubmed.ncbi.nlm.nih.gov/11346808/"}}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Centrally authorised (Forsteo) since 2003; biosimilars since 2017."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved 2002 (Forteo). Two-year lifetime limit and osteosarcoma boxed warning removed in November 2020."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Licensed; NICE-recommended for specific high-risk groups."},{"region":"Australia","status":"Registered, prescription-only","note":"On the ARTG; PBS-subsidised for severe osteoporosis."},{"region":"Canada","status":"Authorised, prescription-only","note":"Health Canada-authorised."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Parathyroid hormone analogues are not on the Prohibited List."}],"faq":[{"q":"Is teriparatide a steroid?","a":"No. It is a peptide hormone fragment — 34 amino acids of parathyroid hormone — with no anabolic-steroid activity. 'Anabolic' here means it builds bone."},{"q":"Why was there a two-year limit?","a":"Rats given lifelong high doses developed osteosarcoma. Twenty years of human use found no excess, and the FDA removed the limit and the boxed warning in 2020. Many prescribers still use two-year courses, followed by a drug that holds the gain."},{"q":"Is it better than bisphosphonates?","a":"For severe osteoporosis, the head-to-head VERO trial found fewer new spinal fractures with teriparatide than with risedronate. It is more expensive, injected daily, and usually followed by a bisphosphonate anyway."}],"references":[{"cite":"Neer RM, Arnaud CD, Zanchetta JR, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.","where":"N Engl J Med, 2001","url":"https://pubmed.ncbi.nlm.nih.gov/11346808/","note":"Fracture Prevention Trial; 1,637 women; the approval trial."},{"cite":"Kendler DL, Marin F, Zerbini CAF, et al. Effects of teriparatide and risedronate on new fractures in post-menopausal women with severe osteoporosis (VERO): a multicentre, double-blind, double-dummy, randomised controlled trial.","where":"Lancet, 2018","url":"https://pubmed.ncbi.nlm.nih.gov/?term=VERO+teriparatide+risedronate+Kendler+Lancet+2018","note":"Head-to-head; 1,360 women; 24 months."},{"cite":"Teriparatide (Forteo) prescribing information — 2020 label update removing the two-year limit and boxed warning.","where":"FDA","url":"https://www.accessdata.fda.gov/scripts/cder/daf/","note":"Regulatory status."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade A on the Fracture Prevention Trial and VERO."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"leuprolide","name":"Leuprolide (leuprorelin)","aliases":["Lupron","leuprorelin","Eligard","Prostap","GnRH agonist","LHRH agonist"],"url":"https://lyoresearch.com/compounds/leuprolide","class":{"id":"reproductive-hormones","name":"Reproductive and neuroendocrine hormones","url":"https://lyoresearch.com/classes/reproductive-hormones"},"summary":"Leuprolide is a modified version of GnRH that, given continuously, does the opposite of the natural pulsed hormone: after a brief surge it exhausts the pituitary and shuts down testosterone or oestrogen production almost completely. That makes it a mainstay of advanced prostate cancer, where the 1984 trial that launched it matched the standard oestrogen treatment with far fewer side effects; it is also used for endometriosis, fibroids, central precocious puberty and IVF cycle control. It is a prescription medicine everywhere and prohibited for male athletes.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"Randomised trials since 1984; decades of use","regulatory_status":"Approved (Rx)","molecule":{"formula":"C59H84N16O12","molecular_weight":"1209.4","cas":"53714-56-0","pubchem_cid":657181,"note":null},"pharmacokinetics":{"basis":"label","route":"Intramuscular depot injection, every 1, 3, 4 or 6 months","half_life":"About 3 hours (the peptide itself, intravenous)","licensed_regimen":"7.5 mg IM every 4 weeks, 22.5 mg every 12 weeks, 30 mg every 16 weeks, or 45 mg every 24 weeks (advanced prostate cancer)","product":"Lupron Depot","source":{"title":"Lupron Depot prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cbc8f94e-7330-4465-05ad-16d64493a5dd"}},"outcomes":[{"outcome":"Metastatic prostate cancer (hormone suppression)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"RCT vs DES (n=199) + 40 years of trials","evidence":"Objective response in 86% against 85% on diethylstilbestrol, with equivalent testosterone suppression and fewer serious side effects — the trial that made GnRH agonists the standard of care.","references":[{"citation":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","where":"N Engl J Med, 1984","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/"}],"verbatim":{"text":"Overall, 86 per cent of the leuprolide group had an objective response (complete response, 1 per cent; partial response, 37 per cent; stable disease, 48 per cent), as compared with 85 per cent of the DES group (complete, 2 per cent; partial, 44 per cent; stable, 39 per cent).","citation":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/"}},{"outcome":"Testosterone suppression to castrate levels","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Approval-grade","evidence":"Reliable suppression to castrate range within weeks, after an initial surge — the pharmacology every indication rests on.","references":[{"citation":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","where":"N Engl J Med, 1984","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/"},{"citation":"Leuprolide acetate (Lupron Depot) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Central precocious puberty","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Approval-grade programmes","evidence":"Halts pubertal progression in children with early central puberty; a licensed indication in every major market.","references":[{"citation":"Leuprolide acetate (Lupron Depot) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Endometriosis and uterine fibroids","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Multiple RCTs","evidence":"Reduces pain and lesion or fibroid volume by inducing a reversible low-oestrogen state; use is limited by bone loss and menopausal symptoms, usually to six months with add-back therapy.","references":[{"citation":"Leuprolide acetate (Lupron Depot) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"Same trials + surveillance","evidence":"The consequences of hormone deprivation: hot flushes, loss of libido and bone density, muscle loss, fatigue, and in men a cardiovascular and metabolic risk signal with long-term use. The initial hormone surge can worsen symptoms in the first weeks.","references":[{"citation":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","where":"N Engl J Med, 1984","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/"},{"citation":"Leuprolide acetate (Lupron Depot) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}],"verbatim":{"text":"The leuprolide group reported more \"hot flashes\" (P = 0.00001).","citation":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/"}}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Authorised in every member state for prostate cancer, endometriosis, fibroids and precocious puberty."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved since 1985 (Lupron); multiple depot products."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Licensed (Prostap and others)."},{"region":"Australia","status":"Registered, prescription-only","note":"On the ARTG (Lucrin, Eligard)."},{"region":"Canada","status":"Authorised, prescription-only","note":"Health Canada-authorised."},{"region":"Sport (WADA)","status":"Prohibited at all times (males)","note":"Leuprorelin is named on the Prohibited List among gonadotrophin-releasing factors, prohibited in males."}],"faq":[{"q":"Does leuprolide raise or lower testosterone?","a":"Both, in order: a surge for one to two weeks, then suppression to castrate levels for as long as it is given. The surge is why prostate-cancer patients are often covered with an anti-androgen at the start."},{"q":"Is leuprolide the same as gonadorelin?","a":"No — opposite effects from the same receptor. Gonadorelin is the natural hormone and needs pulsing to work; leuprolide is a long-acting analogue whose continuous presence shuts the axis down."},{"q":"Is it reversible?","a":"Yes. Hormone production resumes after the depot wears off, over weeks to months depending on the formulation and duration of use."}],"references":[{"cite":"The Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer.","where":"N Engl J Med, 1984","url":"https://pubmed.ncbi.nlm.nih.gov/6436700/","note":"199 men; the trial that established GnRH agonists in prostate cancer."},{"cite":"Leuprolide acetate (Lupron Depot) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/","note":"Licensed indications."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade A across licensed indications."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"pramlintide","name":"Pramlintide","aliases":["Symlin","amylin analogue","AC137"],"url":"https://lyoresearch.com/compounds/pramlintide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Pramlintide is a synthetic analogue of amylin, the hormone the pancreas releases with insulin to slow digestion and signal fullness. It is approved in the United States — and nowhere else — as an injection taken with meals alongside insulin in type 1 and type 2 diabetes. In people with obesity but no diabetes, a 12-month trial produced about 6–7 kg of placebo-corrected weight loss at the best doses, with nausea in up to a third at the start. It was never a commercial success, but its mechanism is the one cagrilintide and amycretin have since made weekly.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"Approval programme + 12-month obesity RCT (n=411)","regulatory_status":"Approved (Rx, US only)","molecule":{"formula":"C171H267N51O53S2","molecular_weight":"3949","cas":"151126-32-8","pubchem_cid":70691388,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, before each major meal","half_life":"About 48 minutes","licensed_regimen":"Type 1: 15 mcg before major meals, increased in 15 mcg steps to 30 or 60 mcg; Type 2: 60 mcg before major meals, increased to 120 mcg","product":"Symlin","source":{"title":"Symlin prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff"}},"outcomes":[{"outcome":"Blood glucose (with insulin)","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"Approval programme (type 1 and type 2)","evidence":"Modest HbA1c reductions of a few tenths of a point when added to insulin, with lower post-meal glucose excursions; the licensed indication.","references":[{"citation":"Pramlintide acetate (Symlin) prescribing information.","where":"FDA","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Body weight (obesity without diabetes)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 RCT (n=411) with 8-month extension","evidence":"Three-times-daily and higher twice-daily doses produced 3 kg more loss than placebo at four months and 6–7 kg at twelve, with placebo regaining and pramlintide maintaining. Never pursued to approval for obesity.","references":[{"citation":"Smith SR, Aronne LJ, Burns CM, et al. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity.","where":"Diabetes Care, 2008","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Smith+pramlintide+sustained+weight+loss+12-month+lifestyle+intervention+obesity+2008"}],"verbatim":{"text":"Placebo-corrected weight loss with 120 microg t.i.d. and 360 microg b.i.d. averaged 3.2 +/- 1.2 kg (3.1 +/- 1.1% body wt) and 3.3 +/- 1.1 kg (3.1 +/- 1.0% body wt), respectively, at month 4 (both P < 0.01; 4-month evaluable n = 270) and 6.1 +/- 2.1 kg (5.6 +/- 2.1% body wt) and 7.2 +/- 2.3 kg (6.8 +/- 2.3% body wt), respectively, at month 12 (both P < 0.01; 12-month evaluable n = 146).","citation":"Smith SR, Aronne LJ, Burns CM, et al. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity.","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Smith+pramlintide+sustained+weight+loss+12-month+lifestyle+intervention+obesity+2008"}},{"outcome":"Body weight (diabetes, with insulin)","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"Approval programme","evidence":"One to two kilograms less than insulin alone — meaningful because insulin usually adds weight.","references":[{"citation":"Pramlintide acetate (Symlin) prescribing information.","where":"FDA","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"Same trials","evidence":"Nausea in a large minority early on, fading with time; and, when combined with insulin, a risk of severe hypoglycaemia that carries a boxed warning in the US label.","references":[{"citation":"Smith SR, Aronne LJ, Burns CM, et al. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity.","where":"Diabetes Care, 2008","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Smith+pramlintide+sustained+weight+loss+12-month+lifestyle+intervention+obesity+2008"},{"citation":"Pramlintide acetate (Symlin) prescribing information.","where":"FDA","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}],"verbatim":{"text":"Nausea, the most common adverse event with pramlintide in the 4-month study (9-29% pramlintide vs. 2% placebo), was generally mild to moderate and occurred in <10% of subjects during the extension.","citation":"Smith SR, Aronne LJ, Burns CM, et al. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity.","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Smith+pramlintide+sustained+weight+loss+12-month+lifestyle+intervention+obesity+2008"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"A marketing application was withdrawn; no EU approval."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved 2005 (Symlin) for type 1 and type 2 diabetes using mealtime insulin. Boxed warning for insulin-induced severe hypoglycaemia."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence."},{"region":"Australia","status":"Not registered","note":"Not on the ARTG."},{"region":"Canada","status":"Not authorised","note":"No Health Canada authorisation."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the Prohibited List."}],"faq":[{"q":"Is pramlintide a weight-loss drug?","a":"It causes modest weight loss — about 6–7 kg placebo-corrected over a year in its one obesity trial — but was never approved for that use and is far weaker than GLP-1 drugs. Its descendant cagrilintide, combined with semaglutide, is the modern version."},{"q":"Why is it only approved in the US?","a":"The European application was withdrawn and it was never pursued elsewhere. Three daily injections and a hypoglycaemia warning made it a niche product even in the US."},{"q":"How does it relate to cagrilintide?","a":"Same target — the amylin receptor — but pramlintide lasts hours and needs dosing with each meal, while cagrilintide is engineered to last a week. Pramlintide proved the mechanism; cagrilintide made it practical."}],"references":[{"cite":"Smith SR, Aronne LJ, Burns CM, et al. Sustained weight loss following 12-month pramlintide treatment as an adjunct to lifestyle intervention in obesity.","where":"Diabetes Care, 2008","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Smith+pramlintide+sustained+weight+loss+12-month+lifestyle+intervention+obesity+2008","note":"411 obese adults without diabetes; 4-month RCT plus 8-month extension."},{"cite":"Pramlintide acetate (Symlin) prescribing information.","where":"FDA","url":"https://www.accessdata.fda.gov/scripts/cder/daf/","note":"Licensed indications, glucose and weight data, boxed warning."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade A for the licensed diabetes use; B for obesity on a single trial."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"octreotide","name":"Octreotide","aliases":["Sandostatin","Sandostatin LAR","somatostatin analogue","SMS 201-995"],"url":"https://lyoresearch.com/compounds/octreotide","class":{"id":"endocrine-medicines","name":"Bone and endocrine peptide medicines","url":"https://lyoresearch.com/classes/endocrine-medicines"},"summary":"Octreotide is an eight-amino-acid analogue of somatostatin, the hormone that inhibits growth hormone, insulin, glucagon and most gut hormones. Native somatostatin lasts two minutes; octreotide lasts hours, and a monthly depot lasts a month. It is the standard treatment for acromegaly — growth-hormone excess from a pituitary tumour — and for the flushing and diarrhoea of hormone-secreting neuroendocrine tumours. In the PROMID trial it more than doubled the time before such tumours progressed. It is prescription-only everywhere and, as the drug that suppresses growth hormone, sits at the opposite pole from the secretagogues sold on the grey market.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"PROMID RCT (n=85) + approval programmes + decades of use","regulatory_status":"Approved (Rx)","molecule":{"formula":"C49H66N10O10S2","molecular_weight":"1019.2","cas":"83150-76-9","pubchem_cid":448601,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection (or IV), 2-4 times daily; monthly depot (Sandostatin LAR)","half_life":"About 1.7-1.9 hours","licensed_regimen":"Acromegaly: 50 mcg three times daily initially, maintenance 100-500 mcg three times daily; carcinoid tumours: 100-600 mcg/day in 2-4 divided doses","product":"Sandostatin (immediate-release injection)","source":{"title":"Sandostatin injection prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4e2c9856-1836-49f0-9472-4dbeeb408f39"}},"outcomes":[{"outcome":"Acromegaly (growth hormone and IGF-1 control)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Approval-grade programmes; many RCTs","evidence":"Normalises IGF-1 in roughly half of patients and shrinks the pituitary tumour in a majority; first-line medical therapy after or instead of surgery.","references":[{"citation":"Octreotide (Sandostatin, Sandostatin LAR) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Carcinoid syndrome symptoms","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Approval-grade","evidence":"Reliable control of flushing and diarrhoea from hormone-secreting neuroendocrine tumours — the 1988 approval indication.","references":[{"citation":"Octreotide (Sandostatin, Sandostatin LAR) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]},{"outcome":"Tumour progression in midgut neuroendocrine tumours","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"1 placebo-controlled RCT (n=85)","evidence":"Time to progression rose from 6 to 14.3 months against placebo, in functionally active and inactive tumours alike; survival could not be assessed because too few patients died.","references":[{"citation":"Rinke A, Müller HH, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group.","where":"J Clin Oncol, 2009","url":"https://pubmed.ncbi.nlm.nih.gov/19704057/"}],"verbatim":{"text":"Median time to tumor progression in the octreotide LAR and placebo groups was 14.3 and 6 months, respectively (hazard ratio [HR] = 0.34; 95% CI, 0.20 to 0.59; P = .000072).","citation":"Rinke A, Müller HH, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group.","url":"https://pubmed.ncbi.nlm.nih.gov/19704057/"}},{"outcome":"Overall survival in neuroendocrine tumours","grade":"B","grade_meaning":"probable, not settled","effect_size":"not measurable","adverse":false,"human_studies":"PROMID (underpowered)","evidence":"A non-significant trend with only 16 deaths at interim; the long-term follow-up remained inconclusive, partly because most placebo patients crossed over.","references":[{"citation":"Rinke A, Müller HH, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group.","where":"J Clin Oncol, 2009","url":"https://pubmed.ncbi.nlm.nih.gov/19704057/"}],"verbatim":{"text":"The HR for overall survival was 0.81 (95% CI, 0.30 to 2.18).","citation":"Rinke A, Müller HH, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group.","url":"https://pubmed.ncbi.nlm.nih.gov/19704057/"}},{"outcome":"Adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"Decades of use","evidence":"Gallstones in a substantial share of long-term users, abdominal cramps and fatty stools, injection-site pain, and disturbed glucose control in either direction.","references":[{"citation":"Octreotide (Sandostatin, Sandostatin LAR) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Authorised in every member state (Sandostatin, LAR) for acromegaly, neuroendocrine tumours and other indications."},{"region":"United States","status":"Approved, prescription-only","note":"FDA-approved since 1988; LAR depot 1998; generics available."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Licensed."},{"region":"Australia","status":"Registered, prescription-only","note":"On the ARTG."},{"region":"Canada","status":"Authorised, prescription-only","note":"Health Canada-authorised."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Somatostatin analogues are not on the Prohibited List."}],"faq":[{"q":"What is octreotide used for?","a":"Mainly acromegaly — growth-hormone excess from a pituitary tumour — and the symptoms and growth of hormone-secreting neuroendocrine tumours. Also variceal bleeding, fistulas and dumping syndrome, and as a radiolabelled agent for imaging and therapy."},{"q":"Does it shrink tumours?","a":"It shrinks pituitary tumours in acromegaly in most patients, and in midgut neuroendocrine tumours it mostly stabilises rather than shrinks — time to progression more than doubled in PROMID, with few outright responses."},{"q":"Is it the opposite of the growth-hormone peptides?","a":"In effect, yes. The secretagogues and GHRH analogues push growth hormone up; octreotide is the approved medicine for pushing it down when the body makes too much."}],"references":[{"cite":"Rinke A, Müller HH, Schade-Brittinger C, et al. Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group.","where":"J Clin Oncol, 2009","url":"https://pubmed.ncbi.nlm.nih.gov/19704057/","note":"85 patients; interim analysis at 67 progressions."},{"cite":"Octreotide (Sandostatin, Sandostatin LAR) prescribing information and approved indications.","where":"FDA / EMA product information","url":"https://www.accessdata.fda.gov/scripts/cder/daf/","note":"Licensed indications; acromegaly and carcinoid data."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade A on approval programmes and PROMID."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"peg-mgf","name":"PEG-MGF","aliases":["mechano growth factor","MGF","IGF-1Ec","pegylated mechano growth factor"],"url":"https://lyoresearch.com/compounds/peg-mgf","class":{"id":"growth-hormone-and-igf","name":"Growth hormone, IGF-1 and growth factors","url":"https://lyoresearch.com/classes/growth-hormone-and-igf"},"summary":"Mechano growth factor is a splice variant of IGF-1 that muscle makes briefly after loading or damage; its distinctive tail is thought to signal muscle stem cells to divide. PEG-MGF is a synthetic version of that tail with polyethylene glycol attached to make it last longer, sold for muscle repair and growth. No human study has ever administered it: the entire human literature measures how much MGF muscle expresses after exercise, growth hormone or ultrasound. It is not approved anywhere and is named on the Prohibited List.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 — every human study measures the body's own MGF","regulatory_status":"Not approved; research reagent","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"A pegylated peptide with no single defined structure in public databases"},"pharmacokinetics":{"basis":"none","route":"Injected as sold; no human study","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Muscle growth or repair (injected)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"No human study of any design has given MGF or PEG-MGF. Claims rest on rodent injections and on human studies that only measured natural MGF expression.","references":[{"citation":"Hameed M, Lange KH, Andersen JL, et al. The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men.","where":"J Physiol, 2004","url":"https://pubmed.ncbi.nlm.nih.gov/14565994/"},{"citation":"Searches of PubMed and trial registries for administered mechano growth factor or PEG-MGF in humans.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=%22mechano+growth+factor%22+human"}]},{"outcome":"MGF expression after exercise (the body's own)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Several small physiology studies","evidence":"Human muscle raises MGF messenger RNA after resistance exercise and growth hormone, more in young than old. Real and interesting; it says nothing about injecting a synthetic fragment.","references":[{"citation":"Hameed M, Lange KH, Andersen JL, et al. The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men.","where":"J Physiol, 2004","url":"https://pubmed.ncbi.nlm.nih.gov/14565994/"}]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"None","evidence":"Unknown. A long-acting IGF-1-derived peptide would be expected to share IGF-1's concerns, including effects on glucose and on cell proliferation, and none of that has been measured.","references":[]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation anywhere. Supplying it for human use is an offence under national medicines law."},{"region":"United States","status":"Not approved","note":"Research reagent 'not for human use'; no clinical programme."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Mechano growth factors are named on the Prohibited List under growth factors (S2), in and out of competition."}],"faq":[{"q":"Does PEG-MGF build muscle?","a":"Nobody knows. It has never been given to a human in any study. The rodent injections that drive the claim used the peptide in muscle directly, not a pegylated version in the blood."},{"q":"Is MGF real?","a":"Yes — as something muscle makes after loading. Human studies have measured it for twenty years. That is a fact about physiology, not about a product."},{"q":"Is it legal?","a":"It is not an approved medicine anywhere, and it is explicitly named on the WADA list. Selling it for human use is an offence in the EU and UK."}],"references":[{"cite":"Hameed M, Lange KH, Andersen JL, et al. The effect of recombinant human growth hormone and resistance training on IGF-I mRNA expression in the muscles of elderly men.","where":"J Physiol, 2004","url":"https://pubmed.ncbi.nlm.nih.gov/14565994/","note":"Measures natural MGF expression; nothing administered."},{"cite":"Searches of PubMed and trial registries for administered mechano growth factor or PEG-MGF in humans.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=%22mechano+growth+factor%22+human","note":"No human administration study identified."},{"cite":"Dominikowski A, et al. The emerging landscape of performance-enhancing peptides modulating GH-IGF1 axis: bridging the gap between clinical evidence and patient self-administration.","where":"Front Endocrinol, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42395176/","note":"Review of the evidence gap across the class."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade D: no human administration study exists."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"adipotide","name":"Adipotide","aliases":["FTPP","prohibitin-TP01","fat-targeted proapoptotic peptide","CKGGRAKDC-GG-D(KLAKLAK)2"],"url":"https://lyoresearch.com/compounds/adipotide","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"Adipotide is a two-part synthetic peptide: a homing sequence that binds a protein on the blood vessels of white fat, joined to a fragment that triggers cell death. Cut off the blood supply and the fat tissue shrinks. In obese monkeys it produced rapid weight loss and better insulin sensitivity — and dose-dependent, reversible kidney damage. A human phase 1 trial in prostate cancer was registered in 2010 and no result was ever published. It is sold online as a fat-loss peptide on the strength of the monkey study. It is not approved anywhere and is prohibited in sport.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 published; a phase 1 in prostate cancer was registered and never reported","regulatory_status":"Not approved; investigational (stalled)","molecule":{"formula":"C111H206N36O28S2","molecular_weight":"2557.2","cas":"859216-15-2","pubchem_cid":163360068,"note":null},"pharmacokinetics":{"basis":"none","route":"Injected as sold; monkeys only","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Fat loss (humans)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 published","evidence":"No human efficacy or safety data exists in the literature. The registered phase 1 (prostate cancer, not obesity) has no published result.","references":[{"citation":"Barnhart KF, Christianson DR, Hanley PW, et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.","where":"Sci Transl Med, 2011","url":"https://pubmed.ncbi.nlm.nih.gov/22072637/"},{"citation":"Searches of PubMed and ClinicalTrials.gov for adipotide in humans.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=adipotide"}]},{"outcome":"Fat loss (obese primates)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Preclinical only","evidence":"Obese rhesus monkeys lost weight rapidly and improved insulin resistance, with imaging confirming loss of white fat — the result the product is sold on. Grade D because it is not human evidence.","references":[{"citation":"Barnhart KF, Christianson DR, Hanley PW, et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.","where":"Sci Transl Med, 2011","url":"https://pubmed.ncbi.nlm.nih.gov/22072637/"}]},{"outcome":"Kidney toxicity (primates)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"Preclinical only","evidence":"At effective doses, monkeys of three species showed predictable, dose-dependent changes in proximal tubule function that reversed when treatment stopped. The mechanism — the homing sequence also binds in the kidney — is the reason development stalled and the reason human use without monitoring is reckless.","references":[{"citation":"Barnhart KF, Christianson DR, Hanley PW, et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.","where":"Sci Transl Med, 2011","url":"https://pubmed.ncbi.nlm.nih.gov/22072637/"}]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"No marketing authorisation anywhere. Supplying it for human use is an offence under national medicines law."},{"region":"United States","status":"Not approved","note":"Investigational; one registered phase 1 with no reported result. Sold as a 'research chemical'."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG; imports are seized."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"As a non-approved substance it falls under the non-approved-substances class, prohibited in and out of competition."}],"faq":[{"q":"Does adipotide work for fat loss?","a":"In obese monkeys, dramatically. In humans, nobody knows: no result has ever been published. The monkey study also found kidney damage at effective doses."},{"q":"Is adipotide safe?","a":"The only safety data is from monkeys, where it caused dose-dependent kidney tubule damage that reversed on stopping. Whether that holds in humans, at grey-market doses, without monitoring, has never been tested."},{"q":"Why was it never developed?","a":"The kidney toxicity, most likely: the peptide that homes to fat vessels also binds in the kidney. A human phase 1 was registered in 2010 and no result appeared."}],"references":[{"cite":"Barnhart KF, Christianson DR, Hanley PW, et al. A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.","where":"Sci Transl Med, 2011","url":"https://pubmed.ncbi.nlm.nih.gov/22072637/","note":"Rhesus and other monkeys; preclinical; reversible kidney toxicity reported."},{"cite":"Searches of PubMed and ClinicalTrials.gov for adipotide in humans.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=adipotide","note":"Seven PubMed results, none clinical; the registered phase 1 (prostate cancer) has no published result."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade D: primate data only; kidney signal recorded."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"ahk-cu","name":"AHK-Cu","aliases":["copper tripeptide AHK","Ala-His-Lys copper","alanyl-histidyl-lysine copper","copper peptide (hair)"],"url":"https://lyoresearch.com/compounds/ahk-cu","class":{"id":"healing-peptides","name":"Tissue-repair peptides","url":"https://lyoresearch.com/classes/healing-peptides"},"summary":"AHK-Cu is a copper-bound tripeptide — alanine, histidine, lysine — marketed for hair growth in serums and, increasingly, as an injectable alongside GHK-Cu. The entire evidence base is one 2007 laboratory study in which it lengthened human hair follicles kept alive in culture and made dermal papilla cells divide. No trial has applied it to a person's scalp, let alone injected it. It is a legal cosmetic ingredient and nothing more; GHK-Cu, by contrast, has small human trials for topical skin use.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 — one ex vivo follicle study","regulatory_status":"Cosmetic ingredient; no clinical evidence","molecule":{"formula":"C15H24ClCuN6O4-","molecular_weight":"451.39","cas":"682809-81-0","pubchem_cid":168431292,"note":"PubChem record is the hydrochloride"},"pharmacokinetics":{"basis":"none","route":"Topical as sold; no human study","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Hair growth (topical, in people)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled","evidence":"No human trial of any design. The single study kept plucked human follicles alive in a dish for a week and measured elongation.","references":[{"citation":"Pyo HK, Yoo HG, Won CH, et al. The effect of tripeptide-copper complex on human hair growth in vitro.","where":"Arch Pharm Res, 2007","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Pyo+tripeptide-copper+complex+human+hair+growth+in+vitro+2007"},{"citation":"Searches of PubMed and trial registries for AHK-Cu in humans.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=AHK-Cu"}]},{"outcome":"Hair follicle elongation (ex vivo)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"1 laboratory study","evidence":"At nanomolar concentrations AHK-Cu lengthened cultured human follicles and increased dermal papilla cell proliferation; the anti-apoptotic effect it was designed to show was not statistically significant. Laboratory evidence, not clinical.","references":[{"citation":"Pyo HK, Yoo HG, Won CH, et al. The effect of tripeptide-copper complex on human hair growth in vitro.","where":"Arch Pharm Res, 2007","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Pyo+tripeptide-copper+complex+human+hair+growth+in+vitro+2007"}]},{"outcome":"Injected use (skin, hair)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"No study of any kind. An injected copper peptide has no established pharmacology in humans.","references":[]},{"outcome":"Safety in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":true,"human_studies":"Cosmetic-use experience only","evidence":"Topical use as a cosmetic ingredient has no reported safety signal; injected use has no data at all.","references":[]}],"regions":[{"region":"European Union","status":"Cosmetic ingredient","note":"Permitted in cosmetics; no medicinal authorisation. Injectable products are unauthorised medicines."},{"region":"United States","status":"Cosmetic ingredient","note":"Sold in cosmetics without drug approval; injectable versions are unapproved drugs."},{"region":"United Kingdom","status":"Cosmetic ingredient","note":"Same position; injectable use is unlicensed."},{"region":"Australia","status":"Cosmetic ingredient","note":"Topical cosmetic use permitted; injectables not on the ARTG."},{"region":"Canada","status":"Cosmetic ingredient","note":"Topical cosmetic use; no DIN for any injectable."},{"region":"Sport (WADA)","status":"Not named","note":"Not on the Prohibited List."}],"faq":[{"q":"Does AHK-Cu grow hair?","a":"In a dish, it lengthened cultured follicles in one study. On a person, it has never been tested. That is the whole evidence base."},{"q":"AHK-Cu or GHK-Cu?","a":"GHK-Cu has small human trials for topical skin use and a much larger laboratory literature; AHK-Cu has one ex vivo study and nothing in people. For injected use, neither has any human evidence."},{"q":"Is injecting copper peptides safe?","a":"No study has looked. Topical cosmetic use has no known safety signal; injection is a different exposure with no data."}],"references":[{"cite":"Pyo HK, Yoo HG, Won CH, et al. The effect of tripeptide-copper complex on human hair growth in vitro.","where":"Arch Pharm Res, 2007","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Pyo+tripeptide-copper+complex+human+hair+growth+in+vitro+2007","note":"Ex vivo follicles and cultured dermal papilla cells; no human subjects."},{"cite":"Searches of PubMed and trial registries for AHK-Cu in humans.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=AHK-Cu","note":"No clinical study identified."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade D: one ex vivo study, no human trial."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"vip","name":"VIP (vasoactive intestinal peptide)","aliases":["aviptadil","vasoactive intestinal peptide","Zyesami","RLF-100","Invicorp (with phentolamine)"],"url":"https://lyoresearch.com/compounds/vip","class":{"id":"immune-peptides","name":"Immune, antimicrobial and repair-signal peptides","url":"https://lyoresearch.com/classes/immune-peptides"},"summary":"Vasoactive intestinal peptide is a natural hormone that relaxes smooth muscle and blood vessels and dampens inflammation, made throughout the gut, lungs and nervous system. As the drug aviptadil it is licensed in the UK and some other countries — combined with phentolamine as an injection into the penis — for erectile dysfunction. Its pandemic moment came as an intravenous treatment for COVID-19 respiratory failure: the NIH-run TESICO trial of 461 patients was stopped for futility, with no improvement in outcomes or survival. The nasal-spray use promoted for 'chronic inflammatory response syndrome' from mould exposure has never been tested in a controlled trial.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"TESICO RCT (n=461) + earlier sponsor RCT; small trials in ED and pulmonary hypertension","regulatory_status":"Licensed narrowly (ED, some countries); other uses unapproved","molecule":{"formula":"C147H237N43O43S","molecular_weight":"3326.8","cas":"40077-57-4","pubchem_cid":16132300,"note":null},"pharmacokinetics":{"basis":"human","route":"Intravenous infusion (healthy volunteers); intracavernosal in the licensed product","half_life":"About 1 minute (intravenous)","licensed_regimen":null,"product":null,"source":{"title":"Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Gut 1978;19:1049","url":"https://pubmed.ncbi.nlm.nih.gov/730072/"}},"outcomes":[{"outcome":"COVID-19 respiratory failure (intravenous)","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"1 large RCT (n=461) — stopped for futility","evidence":"In the NIH-funded TESICO trial, three days of intravenous aviptadil did not improve the 90-day outcome or survival; the safety monitoring board stopped it for futility. An earlier, smaller sponsor-run trial had reported benefit in some analyses.","references":[{"citation":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","where":"Lancet Respir Med, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/"},{"citation":"Youssef JG, Lavin P, Schoenfeld DA, et al. The use of IV vasoactive intestinal peptide (aviptadil) in patients with critical COVID-19 respiratory failure: results of a 60-day randomized controlled trial.","where":"Crit Care Med, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/36044317/"}],"verbatim":{"text":"The odds ratio (OR) for being in a better category of the primary efficacy endpoint for aviptadil versus placebo at day 90, from a model stratified by baseline disease severity, was 1·11 (95% CI 0·80-1·55; p=0·54).","citation":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/"}},{"outcome":"Survival in COVID-19 respiratory failure","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"TESICO","evidence":"Deaths by day 90 were 38% on aviptadil and 36% on placebo.","references":[{"citation":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","where":"Lancet Respir Med, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/"}],"verbatim":{"text":"The cumulative percentage who died up to day 90 was 38% in the aviptadil group and 36% in the placebo group (hazard ratio 1·04, 95% CI 0·77-1·41; p=0·78).","citation":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/"}},{"outcome":"Erectile dysfunction (intracavernosal, with phentolamine)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"Licensing trials","evidence":"The combination injection produces erections sufficient for intercourse in a majority of men in the trials behind its UK and Danish licences; a niche option where PDE5 inhibitors fail or are unsuitable.","references":[{"citation":"Invicorp (aviptadil / phentolamine) — Summary of Product Characteristics.","where":"MHRA / emc, UK","url":"https://www.medicines.org.uk/emc/search?q=invicorp"}]},{"outcome":"Pulmonary hypertension (inhaled)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Small studies","evidence":"Inhaled VIP lowered pulmonary pressures acutely in small open studies; a development programme did not reach approval.","references":[{"citation":"Inhaled vasoactive intestinal peptide in pulmonary hypertension — clinical studies.","where":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=inhaled+vasoactive+intestinal+peptide+pulmonary+hypertension"}]},{"outcome":"'Mould illness' / CIRS (nasal spray)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None controlled","evidence":"The use it is most sold for online. No randomised trial exists; the diagnosis itself is not recognised by mainstream medicine. Claims rest on a single practitioner's uncontrolled case series.","references":[{"citation":"Searches of PubMed and trial registries for intranasal VIP in chronic inflammatory response syndrome or mould illness.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=vasoactive+intestinal+peptide+nasal+chronic+inflammatory+response+syndrome"}]},{"outcome":"Adverse effects","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":true,"human_studies":"TESICO + licensing data","evidence":"Flushing, low blood pressure, diarrhoea and fast heart rate with systemic doses; in TESICO the composite safety outcome was numerically worse on aviptadil without reaching significance. Intracavernosal use: pain and prolonged erection.","references":[{"citation":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","where":"Lancet Respir Med, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/"},{"citation":"Invicorp (aviptadil / phentolamine) — Summary of Product Characteristics.","where":"MHRA / emc, UK","url":"https://www.medicines.org.uk/emc/search?q=invicorp"}]}],"regions":[{"region":"European Union","status":"Authorised in some member states (ED, with phentolamine)","note":"Invicorp is licensed nationally in Denmark and others for erectile dysfunction; no authorisation for any other use."},{"region":"United States","status":"Not approved","note":"Emergency authorisation for COVID-19 was sought and not granted; no approved aviptadil product."},{"region":"United Kingdom","status":"Licensed, prescription-only (Invicorp, ED)","note":"Licensed for erectile dysfunction as an intracavernosal injection with phentolamine. Nasal VIP is unlicensed."},{"region":"Australia","status":"Not registered","note":"Not on the ARTG."},{"region":"Canada","status":"Not authorised","note":"No Health Canada authorisation."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the Prohibited List."}],"faq":[{"q":"Did VIP work for COVID-19?","a":"No. The NIH-funded TESICO trial of 461 patients with respiratory failure was stopped for futility: no improvement in recovery and no survival benefit. A smaller sponsor trial had suggested otherwise."},{"q":"Does nasal VIP treat mould illness or CIRS?","a":"There is no controlled trial, and the diagnosis is not recognised by mainstream medicine. The claims come from one practitioner's uncontrolled patient series."},{"q":"Is VIP approved anywhere?","a":"Yes, narrowly: as an injection into the penis, combined with phentolamine, for erectile dysfunction in the UK, Denmark and a few other countries. Not in the US, and not for any inhaled or nasal use."}],"references":[{"cite":"Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial.","where":"Lancet Respir Med, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37348524/","note":"461 patients; stopped for futility."},{"cite":"Youssef JG, Lavin P, Schoenfeld DA, et al. The use of IV vasoactive intestinal peptide (aviptadil) in patients with critical COVID-19 respiratory failure: results of a 60-day randomized controlled trial.","where":"Crit Care Med, 2022","url":"https://pubmed.ncbi.nlm.nih.gov/36044317/","note":"Sponsor-run; the earlier, smaller trial."},{"cite":"Invicorp (aviptadil / phentolamine) — Summary of Product Characteristics.","where":"MHRA / emc, UK","url":"https://www.medicines.org.uk/emc/search?q=invicorp","note":"Licensed use in erectile dysfunction."},{"cite":"Inhaled vasoactive intestinal peptide in pulmonary hypertension — clinical studies.","where":"PubMed search","url":"https://pubmed.ncbi.nlm.nih.gov/?term=inhaled+vasoactive+intestinal+peptide+pulmonary+hypertension","note":"Small studies; no approval."},{"cite":"Searches of PubMed and trial registries for intranasal VIP in chronic inflammatory response syndrome or mould illness.","where":"LYO literature search, September 2026","url":"https://pubmed.ncbi.nlm.nih.gov/?term=vasoactive+intestinal+peptide+nasal+chronic+inflammatory+response+syndrome","note":"No controlled trial identified."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. COVID rows carry a high-certainty null (A, effect none); ED graded B on licensing data; CIRS use D."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"ara-290","name":"ARA-290 (cibinetide)","aliases":["cibinetide","ARA 290","pyroglutamate helix B surface peptide","pHBSP"],"url":"https://lyoresearch.com/compounds/ara-290","class":{"id":"immune-peptides","name":"Immune, antimicrobial and repair-signal peptides","url":"https://lyoresearch.com/classes/immune-peptides"},"summary":"ARA-290 is a short peptide copied from a surface of the erythropoietin molecule that signals tissue protection but not red-cell production. Its developer has run small randomised trials in small-fibre neuropathy, mostly in sarcoidosis: in a 64-person, 28-day phase 2, the 4 mg dose measurably increased nerve fibres in the cornea and skin, while pain improved on placebo as much as on drug. No phase 3 has been completed and it is not approved anywhere. The grey market sells it for pain, healing and inflammation on the strength of that early signal.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"Phase 2 RCTs in sarcoidosis neuropathy (n=64) and diabetes; no phase 3","regulatory_status":"Not approved; investigational","molecule":{"formula":"C51H84N16O21","molecular_weight":"1257.3","cas":"1208243-50-8","pubchem_cid":91810664,"note":null},"pharmacokinetics":{"basis":"none","route":"Intravenous and subcutaneous in the trials, which report no PK","half_life":"No human pharmacokinetic data located","licensed_regimen":null,"product":null,"source":{"title":"Heij L, et al. Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study. Mol Med 2012","url":"https://pubmed.ncbi.nlm.nih.gov/23168581/"}},"outcomes":[{"outcome":"Nerve fibre regeneration (sarcoidosis small-fibre neuropathy)","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 phase 2b RCT (n=64, 28 days)","evidence":"Corneal nerve fibre area rose significantly on the 4 mg dose but not on 1 mg or 8 mg, and regenerating skin fibres increased at 4 mg — a surrogate signal, in a short trial, with a non-monotonic dose response.","references":[{"citation":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","where":"Invest Ophthalmol Vis Sci, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017"}],"verbatim":{"text":"The placebo-corrected mean change from baseline CNFA (μm2) at day 28 was 109 (95% confidence interval [CI], -429, 647), 697 (159, 1236; P = 0.012), and 431 (-130, 992) in the 1, 4, and 8 mg groups, respectively.","citation":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017"}},{"outcome":"Neuropathic pain","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Same trial + earlier phase 2","evidence":"Pain improved in every arm including placebo; the placebo-corrected difference in the 4 mg group did not reach significance.","references":[{"citation":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","where":"Invest Ophthalmol Vis Sci, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017"}],"verbatim":{"text":"Pain improved significantly in all groups, with subjects having moderate-severe pain reporting a clinically meaningful placebo-corrected decrease in pain intensity in the 4 mg group (P = 0.157).","citation":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017"}},{"outcome":"Diabetic neuropathy and metabolic control","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 small phase 2","evidence":"A 28-day trial in type 2 diabetes with neuropathy reported improved HbA1c and neuropathic symptoms; small, short, not replicated.","references":[{"citation":"Brines M, Dunne AN, van Velzen M, et al. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.","where":"Mol Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Brines+ARA+290+type+2+diabetes+neuropathic+symptoms+2015"}]},{"outcome":"Healing, recovery, inflammation (grey-market uses)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None","evidence":"Extrapolated from the mechanism and from animal work. No human trial.","references":[]},{"outcome":"Adverse effects","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":true,"human_studies":"Phase 2 trials","evidence":"Well tolerated in the short trials, with no effect on haemoglobin — the point of the design. No long-term data.","references":[{"citation":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","where":"Invest Ophthalmol Vis Sci, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017"}]}],"regions":[{"region":"European Union","status":"Unauthorised medicinal product","note":"Investigational only; orphan designation. Supplying it for human use outside a trial is an offence."},{"region":"United States","status":"Not approved","note":"Investigational; orphan designation for sarcoidosis neuropathy. Sold as a 'research chemical'."},{"region":"United Kingdom","status":"Unlicensed medicine","note":"No MHRA licence."},{"region":"Australia","status":"Prescription-only / unapproved","note":"Not on the ARTG."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"A non-approved substance under the non-approved-substances class; it is designed not to stimulate red cells, but that does not exempt it."}],"faq":[{"q":"Does ARA-290 help nerve pain?","a":"In the largest trial, pain improved on placebo as much as on the drug. What improved on the drug — at one dose — was the number of nerve fibres measured in the cornea and skin, which is a surrogate that may or may not matter to how a person feels."},{"q":"Is ARA-290 like EPO?","a":"It is a fragment of EPO chosen to keep the tissue-protective signal and drop the red-cell signal. In trials it did not raise haemoglobin, which was the design goal."},{"q":"Is it approved?","a":"No. It has orphan designations and phase 2 data, and no phase 3 result. It is not approved anywhere and is prohibited in sport as a non-approved substance."}],"references":[{"cite":"Culver DA, Dahan A, Bajorunas D, et al. Cibinetide improves corneal nerve fiber abundance in patients with sarcoidosis-associated small nerve fiber loss and neuropathic pain.","where":"Invest Ophthalmol Vis Sci, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Culver+cibinetide+corneal+nerve+fiber+sarcoidosis+2017","note":"Phase 2b; 64 patients; 28 days."},{"cite":"Brines M, Dunne AN, van Velzen M, et al. ARA 290, a nonerythropoietic peptide engineered from erythropoietin, improves metabolic control and neuropathic symptoms in patients with type 2 diabetes.","where":"Mol Med, 2015","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Brines+ARA+290+type+2+diabetes+neuropathic+symptoms+2015","note":"Small 28-day phase 2."}],"last_reviewed":"2026-09-10","literature_searched_to":"2026-09-10","changelog":[{"date":"2026-09-10","note":"Initial publication. Grade C on phase 2 surrogate data; pain did not separate from placebo."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"cagrisema","name":"CagriSema","aliases":["cagrilintide/semaglutide","cagrilintide-semaglutide","NN9838"],"url":"https://lyoresearch.com/compounds/cagrisema","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"CagriSema is a once-weekly co-injection of cagrilintide, an amylin analogue, with semaglutide 2.4 mg. In REDEFINE 1, a 3,417-person phase 3 trial published in 2025, it produced 20.4% average weight loss at 68 weeks against 3.0% on placebo; in people with type 2 diabetes the figure was 13.7%. Both trials are peer-reviewed. It is not yet approved anywhere, and anything sold under the name is not the trial product.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"2 phase 3 RCTs published (n=3,417; n=1,206); 2 further phase 3 topline (Sep 2026)","regulatory_status":"Investigational (filed)","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"A co-formulation of two molecules: see cagrilintide and semaglutide"},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, once weekly (two injections)","half_life":"A combination: cagrilintide about 7–8 days, semaglutide about 1 week","licensed_regimen":null,"product":null,"source":{"title":"Enebo LB, et al. Lancet 2021 (cagrilintide with semaglutide 2.4 mg, phase 1b)","url":"https://www.sciencedirect.com/science/article/abs/pii/S014067362100845X"}},"outcomes":[{"outcome":"Body weight (obesity without diabetes)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"1 phase 3 RCT (n=3,417, 68 wk)","evidence":"REDEFINE 1 randomised 2,108 people to the combination, 302 to semaglutide alone, 302 to cagrilintide alone and 705 to placebo. The combination lost 20.4% against 3.0% on placebo; the single agents landed in between. Published in the New England Journal of Medicine.","references":[{"citation":"Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544433/"}],"verbatim":{"text":"The estimated mean percent change in body weight from baseline to week 68 was -20.4% with cagrilintide-semaglutide as compared with -3.0% with placebo (estimated difference, -17.3 percentage points; 95% confidence interval, -18.1 to -16.6; P<0.001).","citation":"Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","url":"https://pubmed.ncbi.nlm.nih.gov/40544433/"}},{"outcome":"Body weight (obesity with type 2 diabetes)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"1 phase 3 RCT (n=1,206, 68 wk)","evidence":"REDEFINE 2: 13.7% loss against 3.4% on placebo — the usual smaller effect in people with diabetes. Nearly three-quarters reached an HbA1c of 6.5% or below.","references":[{"citation":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/"}],"verbatim":{"text":"The estimated mean change in body weight from baseline to week 68 was -13.7% in the cagrilintide-semaglutide group and -3.4% in the placebo group (estimated difference, -10.4 percentage points; 95% confidence interval, -11.2 to -9.5; P<0.001).","citation":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/"}},{"outcome":"Blood glucose (HbA1c) in type 2 diabetes","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"1 phase 3 RCT (n=1,206)","evidence":"In REDEFINE 2, 73.5% of people on the combination reached an HbA1c of 6.5% or less against 15.9% on placebo.","references":[{"citation":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/"}],"verbatim":{"text":"The percentage of patients who had a glycated hemoglobin level of 6.5% or less was 73.5% in the cagrilintide-semaglutide group and 15.9% in the placebo group.","citation":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/"}},{"outcome":"Body weight (vs tirzepatide 5 mg, type 2 diabetes)","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT topline (REIMAGINE 5, 60 wk)","evidence":"Novo Nordisk press release, 21 September 2026: in adults with type 2 diabetes not controlled on metformin, an SGLT2 inhibitor or both, CagriSema 1.0 mg/1.0 mg produced 12.4% weight loss at 60 weeks against 9.1% on tirzepatide 5 mg, with HbA1c reductions of 1.71 and 1.67 points (non-inferior). Both arms were low doses: tirzepatide's lowest maintenance dose, and less than half the 2.4 mg/2.4 mg of CagriSema used in REDEFINE 1. Efficacy estimand; enrolment not stated; not peer-reviewed, so B. The same release reports 21.0% against 2.0% on placebo at 68 weeks for the 1.0 mg/1.0 mg dose in obesity (REDEFINE 9).","references":[{"citation":"Novo Nordisk. CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial (with REDEFINE 9 topline).","where":"Press release, 21 Sep 2026","url":"https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916774"}]},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"Both phase 3 RCTs","evidence":"Four in five people on the combination had gastrointestinal events in REDEFINE 1, against two in five on placebo; the same pattern in REDEFINE 2 (72.5% vs 34.4%). Mostly transient and mild to moderate, as with the parent drugs.","references":[{"citation":"Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544433/"},{"citation":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/"}],"verbatim":{"text":"Gastrointestinal adverse events (affecting 79.6% in the cagrilintide-semaglutide group and 39.9% in the placebo group), including nausea, vomiting, diarrhea, constipation, or abdominal pain, were mainly transient and mild-to-moderate in severity.","citation":"Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","url":"https://pubmed.ncbi.nlm.nih.gov/40544433/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"Investigational; no EMA authorisation at review."},{"region":"United States","status":"Not approved","note":"Novo Nordisk filed a New Drug Application for weight management in December 2025 and says it expects an FDA decision in the fourth quarter of 2026. Not approved at review; products sold under the name are not the trial drug."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Cagrilintide is unapproved, so the combination falls under S0 (non-approved substances) even though semaglutide is not banned."}],"faq":[{"q":"How much weight do people lose on CagriSema?","a":"20.4% on average at 68 weeks in adults with obesity and without diabetes, against 3.0% on placebo; 13.7% in adults with type 2 diabetes. Both figures are from published phase 3 trials."},{"q":"Is CagriSema better than tirzepatide?","a":"Unknown at full dose. Its 20.4% is close to tirzepatide's 20.9% in SURMOUNT-1, but cross-trial numbers are unreliable, and the direct comparison in obesity (REDEFINE 4) has not reported. In REIMAGINE 5, announced by press release in September 2026, low-dose CagriSema beat tirzepatide's lowest maintenance dose in people with type 2 diabetes: 12.4% against 9.1% at 60 weeks."},{"q":"Is CagriSema available?","a":"No. It is not approved anywhere. Vials sold online under the name are unlicensed and not the trial product."},{"q":"Why did the result disappoint?","a":"Novo Nordisk had projected about 25% weight loss from its phase 2 data. The phase 3 delivered 20.4% — still the best published combination result, but the gap moved the company's share price more than it moved the science."}],"references":[{"cite":"Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544433/","note":"3,417 randomised, 68 weeks. NCT05567796."},{"cite":"Davies MJ, et al. Cagrilintide-semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2).","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40544432/","note":"1,206 randomised, 68 weeks. NCT05394519."},{"cite":"Novo Nordisk. CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial (with REDEFINE 9 topline).","where":"Press release, 21 Sep 2026","url":"https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916774","note":"REIMAGINE 5: 60 weeks, type 2 diabetes, vs tirzepatide 5 mg. REDEFINE 9: 68 weeks, obesity, vs placebo. Topline, efficacy estimand; not peer-reviewed. States the US filing of December 2025 and a decision expected in Q4 2026."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"REIMAGINE 5 and REDEFINE 9 topline results (press release, 21 Sep 2026) added as a new row against tirzepatide 5 mg, graded B; US filing status updated (filed December 2025, decision expected Q4 2026). Overall grade unchanged."},{"date":"2026-09-23","note":"Initial publication from the two published REDEFINE phase 3 trials. Overall grade B (investigational, unapproved); the trial rows are graded A on their own certainty."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"eloralintide","name":"Eloralintide","aliases":["LY3841136","selective amylin receptor agonist"],"url":"https://lyoresearch.com/compounds/eloralintide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Eloralintide is a once-weekly amylin receptor agonist from Eli Lilly, tested on its own and, more recently, paired with tirzepatide. In a 263-person phase 2 trial published in The Lancet in 2025, the top doses produced about 20% weight loss at 48 weeks against 0.4% on placebo. Nausea was dose-dependent and fatigue was unusually common. Added to tirzepatide in a phase 2b trial reported by press release in September 2026, it took weight loss in people with type 2 diabetes from 14.8% to 23.3% at 48 weeks. Phase 3 trials are running; it is not approved anywhere.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"1 phase 2 RCT published (n=263); 1 phase 2b topline with tirzepatide (n=367); phase 3 running","regulatory_status":"Investigational (phase 3)","molecule":{"formula":"C201H319N49O65S2","molecular_weight":"4526","cas":"2883634-40-8","pubchem_cid":175663130,"note":null},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, once weekly","half_life":"Dose-proportional exposure at steady state reported; no half-life figure in the abstract","licensed_regimen":null,"product":null,"source":{"title":"Bhattachar S, et al. Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: phase 1 proof of concept. Diabetes Obes Metab 2026","url":"https://pubmed.ncbi.nlm.nih.gov/41559929/"}},"outcomes":[{"outcome":"Body weight","grade":"C","grade_meaning":"weak human evidence","effect_size":"large","adverse":false,"human_studies":"1 phase 2 RCT (n=263, 48 wk)","evidence":"Six dose regimens against placebo in adults with obesity and no diabetes. Loss ranged from 9% at 1 mg to 20% at 9 mg; placebo lost 0.4%. Efficacy estimand, so participants who stopped are not fully counted.","references":[{"citation":"Billings LK, et al. Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.","where":"Lancet, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/41207310/"}],"verbatim":{"text":"The mean percent change in bodyweight from baseline after 48 weeks (efficacy estimand) was -9% (1 mg, 95% CI -12·6 to -6·3), -12% (3 mg, -14·9 to -9·8), -18% (6 mg, -20·7 to -14·5), -20% (9 mg, -22·7 to -17·5), -20% (6-9 mg, -22·7 to -17·0), and -16% (3-9 mg, -18·6 to -14·1), compared with -0·4% (-2·2 to 1·4) in the placebo group.","citation":"Billings LK, et al. Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/41207310/"}},{"outcome":"Body weight (with tirzepatide, type 2 diabetes)","grade":"C","grade_meaning":"weak human evidence","effect_size":"large","adverse":false,"human_studies":"1 phase 2b RCT topline (n=367, 48 wk)","evidence":"Lilly press release, 30 September 2026, presented at the EASD meeting: in adults with obesity or overweight and type 2 diabetes, eloralintide 9 mg with tirzepatide 15 mg produced 23.3% weight loss at 48 weeks against 14.8% on tirzepatide 15 mg alone and 3.0% on placebo; HbA1c fell 2.9, 2.4 and 0.3 points. Eloralintide alone reached 12.3%. Read with care: 367 people across ten groups, an efficacy estimand, and 10.8–27.0% of the combination groups stopped for adverse events against 2.9% on tirzepatide alone. Not peer-reviewed.","references":[{"citation":"Eli Lilly. EloraTZP (combination of eloralintide and tirzepatide) delivered greater weight loss and A1C reduction vs. tirzepatide 15 mg in adults with obesity and type 2 diabetes.","where":"Press release, 30 Sep 2026","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-eloratzp-combination-eloralintide-and-tirzepatide"}]},{"outcome":"Nausea and fatigue","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":true,"human_studies":"Same RCT","evidence":"Nausea reached 64% at the 6 mg fixed dose and was lower with escalation. Fatigue in up to 46% — a side effect the GLP-1 drugs do not produce at that rate, and one to watch in phase 3.","references":[{"citation":"Billings LK, et al. Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.","where":"Lancet, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/41207310/"}],"verbatim":{"text":"The most common adverse events with eloralintide were nausea (1 mg 11%, 3 mg 13%, 6 mg 64%, 9 mg 33%, 6-9 mg 54%, 3-9 mg 25%, and placebo 14%) and fatigue (1 mg 0%, 3 mg 13%, 6 mg 29%, 9 mg 43%, 6-9 mg 46%, 3-9 mg 21%, and placebo 12%).","citation":"Billings LK, et al. Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.","url":"https://pubmed.ncbi.nlm.nih.gov/41207310/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"Investigational."},{"region":"United States","status":"Not approved","note":"Investigational; phase 3 running. Products sold under the name are not the trial drug."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so S0 (non-approved substances)."}],"faq":[{"q":"Is eloralintide a GLP-1 drug?","a":"No. It acts only on the amylin receptor. That is the point: it tests whether the amylin pathway alone can deliver GLP-1-scale weight loss."},{"q":"How does it compare with cagrilintide?","a":"Cagrilintide alone produced about 10.8% loss at 26 weeks in its phase 2; eloralintide about 20% at 48 weeks. Different trials, different durations, no direct comparison."},{"q":"When will it be approved?","a":"Phase 3 trials are running. No filing has been made; any date is speculation."}],"references":[{"cite":"Billings LK, et al. Eloralintide, a selective amylin receptor agonist for the treatment of obesity: a 48-week phase 2, multicentre, double-blind, randomised, placebo-controlled trial.","where":"Lancet, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/41207310/","note":"263 randomised, 46 US centres. NCT06230523."},{"cite":"Bhattachar S, et al. Eloralintide, a selective, long-acting amylin receptor agonist for treatment of obesity: phase 1 proof of concept.","where":"Diabetes Obes Metab, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/41559929/"},{"cite":"Eli Lilly. EloraTZP (combination of eloralintide and tirzepatide) delivered greater weight loss and A1C reduction vs. tirzepatide 15 mg in adults with obesity and type 2 diabetes.","where":"Press release, 30 Sep 2026","url":"https://investor.lilly.com/news-releases/news-release-details/lillys-eloratzp-combination-eloralintide-and-tirzepatide","note":"Phase 2b, 367 randomised, 48 weeks, US and Argentina. Efficacy estimand; not peer-reviewed. NCT06603571."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"Phase 2b combination result with tirzepatide (press release, 30 Sep 2026) added as a new row, graded C: one small unpublished trial. Overall grade unchanged."},{"date":"2026-09-23","note":"Initial publication from the Lancet phase 2. Grade C for stage."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"maridebart-cafraglutide","name":"Maridebart cafraglutide","aliases":["MariTide","AMG 133","MariTide peptide"],"url":"https://lyoresearch.com/compounds/maridebart-cafraglutide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Maridebart cafraglutide, or MariTide, is an antibody that blocks the GIP receptor with two GLP-1-agonist peptides attached, injected once a month. In a 592-person phase 2 trial published in the New England Journal of Medicine in 2025, people with obesity lost 12–16% at 52 weeks against 2.5% on placebo. Gut side effects were common, less so with dose escalation. Phase 3 trials are running; it is not approved anywhere.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"1 phase 2 RCT (n=592); phase 3 running","regulatory_status":"Investigational (phase 3)","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"A monoclonal antibody conjugated to two GLP-1 peptides — no small-molecule record"},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, every 4 weeks","half_life":"About 14–16 days for the intact molecule (21–24 days total)","licensed_regimen":null,"product":null,"source":{"title":"Véniant MM, et al. A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings. Nat Metab 2024;6:290–303","url":"https://www.nature.com/articles/s42255-023-00966-w"}},"outcomes":[{"outcome":"Body weight (obesity)","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 phase 2 RCT (465 in the obesity cohort, 52 wk)","evidence":"Six dosing regimens of 140–420 mg every four or eight weeks. Intention-to-treat loss ranged from 12.3% to 16.2% against 2.5% on placebo. In the 127-person diabetes cohort, 8.4–12.3% against 1.7%.","references":[{"citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}],"verbatim":{"text":"In the obesity cohort (465 participants; female sex, 63%; mean age, 47.9 years; mean body-mass index [BMI, the weight in kilograms divided by the square of the height in meters], 37.9), the mean percent change in body weight from baseline to week 52 on the basis of the treatment policy estimand (intention-to-treat approach) ranged from -12.3% (95% confidence interval [CI], -15.0 to -9.7) to -16.2% (95% CI, -18.9 to -13.5) with maridebart cafraglutide, as compared with -2.5% (95% CI, -4.2 to -0.7) with placebo.","citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}},{"outcome":"Blood glucose (HbA1c) in type 2 diabetes","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"Same RCT, diabetes cohort (n=127)","evidence":"HbA1c fell 1.2–1.6 points against 0.1 on placebo.","references":[{"citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}],"verbatim":{"text":"The mean change in the glycated hemoglobin level on the basis of the treatment policy estimand in this cohort was -1.2 to -1.6 percentage points in the maridebart cafraglutide groups and 0.1 percentage points in the placebo group.","citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}},{"outcome":"GI side effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":true,"human_studies":"Same RCT","evidence":"Nausea and vomiting were frequent, particularly without dose escalation; the regimens that started low and stepped up were better tolerated, which is why phase 3 uses escalation.","references":[{"citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}],"verbatim":{"text":"Gastrointestinal adverse events were common with maridebart cafraglutide, although less frequent with dose escalation and a lower starting dose.","citation":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"Investigational."},{"region":"United States","status":"Not approved","note":"Investigational; phase 3 running. Products sold as 'MariTide' online are not the trial drug and cannot be, given the manufacturing involved."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so S0 (non-approved substances)."}],"faq":[{"q":"Is MariTide a peptide?","a":"Partly. Two GLP-1 peptides are attached to an antibody. The antibody gives it the month-long half-life; the peptides do the metabolic work."},{"q":"How does MariTide compare with tirzepatide?","a":"Lower weight loss so far (up to 16% at 52 weeks versus tirzepatide's 21% at 72), given monthly rather than weekly, and with the opposite action at the GIP receptor. No direct comparison exists."},{"q":"Can you buy MariTide?","a":"No. It is an investigational antibody conjugate made by Amgen; nothing sold online under the name is the real molecule."}],"references":[{"cite":"Jastreboff AM, et al. Once-monthly maridebart cafraglutide for the treatment of obesity — a phase 2 trial.","where":"N Engl J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40549887/","note":"592 enrolled; obesity and obesity-diabetes cohorts; 52 weeks. NCT05669599."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication from the NEJM phase 2. Grade B."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"ecnoglutide","name":"Ecnoglutide","aliases":["XW003","cAMP-biased GLP-1 agonist"],"url":"https://lyoresearch.com/compounds/ecnoglutide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Ecnoglutide is a once-weekly GLP-1 receptor agonist developed by Sciwind Biosciences in China, engineered to favour the cAMP signalling pathway. In a 664-person phase 3 trial published in 2025, Chinese adults with overweight or obesity lost 13.2% at 40 weeks on the top dose against 0.1% on placebo. Two phase 3 diabetes trials are also published. It is not approved in any region this site covers.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"3 phase 3 RCTs published (obesity n=664; two in diabetes)","regulatory_status":"Investigational (phase 3 published)","molecule":{"formula":"C194H304N48O61","molecular_weight":"4285","cas":"2459531-73-6","pubchem_cid":162625103,"note":null},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, once weekly","half_life":"About 5–6 days at steady state (124–138 hours)","licensed_regimen":null,"product":null,"source":{"title":"Pan H, et al. Discovery of ecnoglutide — a novel, long-acting, cAMP-biased GLP-1 analog. Mol Metab 2023;75:101762","url":"https://www.sciencedirect.com/science/article/pii/S2212877823000960"}},"outcomes":[{"outcome":"Body weight","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 phase 3 RCT (n=664, 40 wk)","evidence":"Three doses against placebo across 36 Chinese centres. Loss of 9.1%, 10.9% and 13.2% at 1.2, 1.8 and 2.4 mg against 0.1% on placebo. Shorter than the 68–72-week Western trials, so not directly comparable.","references":[{"citation":"Ji L, et al. Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.","where":"Lancet Diabetes Endocrinol, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40555243/"}],"verbatim":{"text":"At week 40, the least-squares mean percentage change in bodyweight was -9·1% (SE 0·8) in the ecnoglutide 1·2 mg group, -10·9% (0·9) in the ecnoglutide 1·8 mg group, and -13·2% (0·8) in the ecnoglutide 2·4 mg group versus 0·1% (0·8) in the placebo group, and the respective estimated treatment differences compared with placebo were -9·2% (97% CI -11·0 to -7·5), -11·1% (-13·1 to -9·1), and -13·3% (-15·3 to -11·3), respectively (all p<0·0001).","citation":"Ji L, et al. Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/40555243/"}},{"outcome":"Blood glucose (HbA1c) in type 2 diabetes","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"2 phase 3 RCTs (EECOH-1, EECOH-2)","evidence":"A placebo-controlled monotherapy trial and a 52-week non-inferiority trial against dulaglutide, both published in 2025.","references":[{"citation":"Efficacy and safety of cAMP signalling-biased GLP-1 analogue ecnoglutide monotherapy versus placebo in patients with type 2 diabetes (EECOH-1): a phase 3 trial.","where":"Nat Commun, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/?term=ecnoglutide+EECOH-1+phase+3"},{"citation":"Efficacy and safety of cAMP-biased GLP-1 receptor agonist ecnoglutide versus dulaglutide in patients with type 2 diabetes (EECOH-2): a 52-week non-inferiority phase 3 trial.","where":"Lancet Diabetes Endocrinol, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/?term=ecnoglutide+EECOH-2+dulaglutide"}]},{"outcome":"GI side effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":true,"human_studies":"Same RCTs","evidence":"The class profile. Ten of 499 people on ecnoglutide stopped for adverse events in the obesity trial.","references":[{"citation":"Ji L, et al. Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.","where":"Lancet Diabetes Endocrinol, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40555243/"}],"verbatim":{"text":"The most common adverse events were mild-to-moderate gastrointestinal related events.","citation":"Ji L, et al. Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/40555243/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"No EMA application known at review."},{"region":"United States","status":"Not approved","note":"Not FDA-approved. Products sold under the name are unlicensed."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Not registered."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Not approved by any of the regulators WADA recognises, so S0 (non-approved substances)."}],"faq":[{"q":"What does 'biased' GLP-1 agonist mean?","a":"The molecule is designed to trigger one of the receptor's two signalling pathways (cAMP) more than the other (β-arrestin). The hope is more effect and less receptor fatigue; the trials so far do not test that claim against an unbiased drug."},{"q":"How does ecnoglutide compare with semaglutide?","a":"13.2% at 40 weeks against semaglutide's 14.9% at 68 weeks — different durations, different populations, no direct trial."},{"q":"Is ecnoglutide approved?","a":"Not in the EU, US, UK, Australia or Canada. Its development and regulatory review are in China."}],"references":[{"cite":"Ji L, et al. Efficacy and safety of a biased GLP-1 receptor agonist ecnoglutide in adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.","where":"Lancet Diabetes Endocrinol, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40555243/","note":"664 randomised, 36 Chinese centres, 40 weeks. NCT05813795."},{"cite":"Efficacy and safety of cAMP signalling-biased GLP-1 analogue ecnoglutide monotherapy versus placebo in patients with type 2 diabetes (EECOH-1): a phase 3 trial.","where":"Nat Commun, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/?term=ecnoglutide+EECOH-1+phase+3"},{"cite":"Efficacy and safety of cAMP-biased GLP-1 receptor agonist ecnoglutide versus dulaglutide in patients with type 2 diabetes (EECOH-2): a 52-week non-inferiority phase 3 trial.","where":"Lancet Diabetes Endocrinol, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/?term=ecnoglutide+EECOH-2+dulaglutide"}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication from the Lancet Diabetes & Endocrinology phase 3. Grade B: published phase 3, unapproved, single-country."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"abaloparatide","name":"Abaloparatide","aliases":["Tymlos","Eladynos","BA058","PTHrP(1-34) analogue"],"url":"https://lyoresearch.com/compounds/abaloparatide","class":{"id":"endocrine-medicines","name":"Bone and endocrine peptide medicines","url":"https://lyoresearch.com/classes/endocrine-medicines"},"summary":"Abaloparatide is a 34-amino-acid analogue of parathyroid-hormone-related protein, given as a daily injection for osteoporosis at high fracture risk. In the ACTIVE trial, 2,463 postmenopausal women were randomised to abaloparatide, placebo or open-label teriparatide for 18 months; abaloparatide reduced new vertebral and non-vertebral fractures against placebo and caused less hypercalcaemia than teriparatide. Approved in the US since 2017 and the EU since 2022.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"ACTIVE RCT (n=2,463) + extension","regulatory_status":"Approved (Rx)","molecule":{"formula":"C174H300N56O49","molecular_weight":"3961","cas":"247062-33-5","pubchem_cid":76943386,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, once daily","half_life":"About 1 hour","licensed_regimen":"80 mcg subcutaneously once daily; use beyond 2 years in a lifetime not recommended","product":"Tymlos","source":{"title":"Tymlos prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=712143d9-e21e-4013-bb3b-3426a21060a8"}},"outcomes":[{"outcome":"Vertebral fracture risk (postmenopausal osteoporosis)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"1 large RCT (n=2,463, 18 mo)","evidence":"New morphometric vertebral fractures in 0.6% on abaloparatide against 4.2% on placebo in the published analysis — a relative reduction of about 86%. The abstract reports the direction and refers to the paper's table for the figures.","references":[{"citation":"Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial (ACTIVE).","where":"JAMA, 2016;316:722–733","url":"https://pubmed.ncbi.nlm.nih.gov/27533157/"}],"verbatim":{"text":"Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months.","citation":"Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial (ACTIVE).","url":"https://pubmed.ncbi.nlm.nih.gov/27533157/"}},{"outcome":"Non-vertebral fracture risk","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Same RCT","evidence":"Non-vertebral fractures 2.7% against 4.7% on placebo — a relative reduction of about 43% in the published analysis. Hip fractures were too few to judge.","references":[{"citation":"Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial (ACTIVE).","where":"JAMA, 2016;316:722–733","url":"https://pubmed.ncbi.nlm.nih.gov/27533157/"}]},{"outcome":"Hypercalcaemia (vs teriparatide)","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":true,"human_studies":"Same RCT, prespecified safety endpoint","evidence":"High blood calcium in 3.4% on abaloparatide against 6.4% on teriparatide — about half the rate, and the main claimed advantage over the older drug.","references":[{"citation":"Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial (ACTIVE).","where":"JAMA, 2016;316:722–733","url":"https://pubmed.ncbi.nlm.nih.gov/27533157/"}],"verbatim":{"text":"Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference [RD], −2.96 [95%CI, −5.12 to −0.87]; P = .006).","citation":"Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial (ACTIVE).","url":"https://pubmed.ncbi.nlm.nih.gov/27533157/"}},{"outcome":"Bone mineral density","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Same RCT","evidence":"Density rose at hip, femoral neck and spine against placebo (all P<0.001), with faster hip gains than teriparatide in the published comparison.","references":[{"citation":"Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial (ACTIVE).","where":"JAMA, 2016;316:722–733","url":"https://pubmed.ncbi.nlm.nih.gov/27533157/"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Eladynos, centrally authorised December 2022 after a 2018 refusal."},{"region":"United States","status":"Approved, prescription-only","note":"Tymlos, FDA-approved April 2017; men at high fracture risk added 2022."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Eladynos licensed by the MHRA."},{"region":"Australia","status":"Check the ARTG","note":"LYO did not find an ARTG entry at review; prescription-only if and when registered."},{"region":"Canada","status":"Check Health Canada","note":"LYO did not find a Drug Identification Number at review."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Parathyroid hormone analogues are not on the Prohibited List."}],"faq":[{"q":"Abaloparatide or teriparatide?","a":"Both build bone and both cut spinal fractures by roughly 80% in their trials. Abaloparatide produced less high calcium and does not need refrigeration after first use. No trial has compared fracture rates head-to-head with adequate power."},{"q":"Why did the EMA first refuse it?","a":"In 2018 the committee judged the cardiovascular safety data insufficient — palpitations and a heart-rate rise were more common on the drug. Additional analyses satisfied it in 2022."},{"q":"Is it a steroid?","a":"No. It is a peptide hormone analogue with no anabolic-steroid action; 'anabolic' here means bone-building."}],"references":[{"cite":"Miller PD, Hattersley G, Riis BJ, et al. Effect of abaloparatide vs placebo on new vertebral fractures in postmenopausal women with osteoporosis: a randomized clinical trial (ACTIVE).","where":"JAMA, 2016;316:722–733","url":"https://pubmed.ncbi.nlm.nih.gov/27533157/","note":"2,463 women, 18 months; abaloparatide 80 µg vs placebo vs open-label teriparatide. Fracture percentages are in the paper's table, not the abstract."},{"cite":"Abaloparatide: EMA summary of the Eladynos authorisation (2022) following the 2018 negative opinion.","where":"EMA","url":"https://www.ema.europa.eu/en/medicines/human/EPAR/eladynos","note":"Regulatory history."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade A on ACTIVE."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"calcitonin","name":"Calcitonin (salmon)","aliases":["salcatonin","Miacalcin","Miacalcic","salmon calcitonin nasal spray"],"url":"https://lyoresearch.com/compounds/calcitonin","class":{"id":"endocrine-medicines","name":"Bone and endocrine peptide medicines","url":"https://lyoresearch.com/classes/endocrine-medicines"},"summary":"Calcitonin is a thyroid hormone that lowers blood calcium by slowing bone breakdown; the salmon version, more potent than human, was sold for decades as an osteoporosis nasal spray. Its one large fracture trial found a 33% reduction in spinal fractures at the middle dose and none at the higher one. In 2012–2013 European and other regulators withdrew the nasal spray after meta-analyses found a small excess of cancers, leaving short-term injectable use for Paget's disease and hypercalcaemia.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"PROOF RCT (n=1,255, 5 yr) + regulatory meta-analyses","regulatory_status":"Approved (Rx, restricted)","molecule":{"formula":"C145H240N44O48S2","molecular_weight":"3431.9","cas":"47931-85-1","pubchem_cid":16220016,"note":"Salmon calcitonin (salcatonin)"},"pharmacokinetics":{"basis":"label","route":"Subcutaneous or intramuscular injection; nasal spray","half_life":"About 1 hour","licensed_regimen":"Paget's disease and postmenopausal osteoporosis: 100 USP Units daily SC or IM; hypercalcaemia: 4 USP Units/kg every 12 hours, up to 8 USP Units/kg every 6 hours","product":"Miacalcin (calcitonin salmon) injection","source":{"title":"Miacalcin injection prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=26caf31f-7f7c-48a8-a1ac-35d2ceefda2b"}},"outcomes":[{"outcome":"Vertebral fracture risk (osteoporosis, nasal spray)","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"1 large RCT (n=1,255, 5 yr)","evidence":"PROOF: the 200 IU dose reduced new vertebral fractures by 33%, but the 100 and 400 IU doses did not — no dose–response, and a trial with 60% dropout. Regulators later judged the benefit marginal.","references":[{"citation":"Chesnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence Of Osteoporotic Fractures study (PROOF).","where":"Am J Med, 2000;109:267–276","url":"https://pubmed.ncbi.nlm.nih.gov/10996576/"}],"verbatim":{"text":"The 200-IU dose of salmon calcitonin nasal spray significantly reduced the risk of new vertebral fractures by 33% compared with placebo [200 IU: 51 of 287, placebo: 70 of 270, relative risk (RR) = 0.67, 95% confidence interval (CI): 0.47- to 0.97, P = 0.03].","citation":"Chesnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence Of Osteoporotic Fractures study (PROOF).","url":"https://pubmed.ncbi.nlm.nih.gov/10996576/"}},{"outcome":"Dose–response","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"Same RCT","evidence":"Neither the lower nor the higher dose separated from placebo — the finding that made the 200 IU result hard to trust.","references":[{"citation":"Chesnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence Of Osteoporotic Fractures study (PROOF).","where":"Am J Med, 2000;109:267–276","url":"https://pubmed.ncbi.nlm.nih.gov/10996576/"}],"verbatim":{"text":"The reductions in vertebral fractures in the 100-IU (RR = 0.85, 95% CI: 0.60- to 1.21) and the 400-IU (RR = 0.84, 95% CI: 0.59- to 1.18) groups were not significantly different from placebo.","citation":"Chesnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence Of Osteoporotic Fractures study (PROOF).","url":"https://pubmed.ncbi.nlm.nih.gov/10996576/"}},{"outcome":"Cancer risk (long-term use)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"Regulatory meta-analyses of RCTs","evidence":"The EMA's 2012 review of randomised trials found a higher proportion of cancers in people on calcitonin than on placebo (about 2.4% excess for the nasal spray over long-term use). The signal is small and the mechanism unknown, but it was enough to end chronic use.","references":[{"citation":"European Medicines Agency. European Medicines Agency recommends limiting long-term use of calcitonin medicines (press release, 20 July 2012).","where":"EMA","url":"https://www.ema.europa.eu/en/news/european-medicines-agency-recommends-limiting-long-term-use-calcitonin-medicines"}]},{"outcome":"Paget's disease and acute hypercalcaemia","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Decades of use; older trials","evidence":"Injectable calcitonin still has short-term licences for Paget's disease, acute bone loss from immobilisation and hypercalcaemia of malignancy, where bisphosphonates have largely replaced it.","references":[{"citation":"European Medicines Agency. European Medicines Agency recommends limiting long-term use of calcitonin medicines (press release, 20 July 2012).","where":"EMA","url":"https://www.ema.europa.eu/en/news/european-medicines-agency-recommends-limiting-long-term-use-calcitonin-medicines"}]}],"regions":[{"region":"European Union","status":"Restricted","note":"Nasal spray marketing authorisations withdrawn following the EMA's July 2012 review; injectable use limited to short courses for Paget's disease, acute immobilisation bone loss and hypercalcaemia of malignancy."},{"region":"United States","status":"Approved, prescription-only","note":"Miacalcin injection and nasal spray remain approved; an FDA advisory committee voted in March 2013 that the nasal spray's benefit for osteoporosis did not outweigh the cancer risk, and the label carries a malignancy warning."},{"region":"United Kingdom","status":"Restricted","note":"Nasal spray withdrawn in 2012 in line with the EMA decision; injection retained for short-term indications."},{"region":"Australia","status":"Restricted","note":"Nasal spray products for osteoporosis were withdrawn; injectable use restricted."},{"region":"Canada","status":"Restricted","note":"Health Canada withdrew nasal calcitonin for osteoporosis in 2013."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the Prohibited List."}],"faq":[{"q":"Why was calcitonin nasal spray withdrawn?","a":"A regulatory meta-analysis of randomised trials found more cancers in people on calcitonin than on placebo, and the fracture benefit for osteoporosis was small and inconsistent. The EMA judged the balance unfavourable for long-term use in 2012."},{"q":"Is calcitonin still used?","a":"Yes, short-term by injection — for Paget's disease, hypercalcaemia and acute bone loss from immobilisation — and in the US the nasal spray is still sold with a warning."},{"q":"Is calcitonin a peptide?","a":"Yes — 32 amino acids with a disulfide ring at one end. The salmon version is the medicine because it is far more potent than human calcitonin."}],"references":[{"cite":"Chesnut CH 3rd, Silverman S, Andriano K, et al. A randomized trial of nasal spray salmon calcitonin in postmenopausal women with established osteoporosis: the Prevent Recurrence Of Osteoporotic Fractures study (PROOF).","where":"Am J Med, 2000;109:267–276","url":"https://pubmed.ncbi.nlm.nih.gov/10996576/","note":"1,255 women, 5 years; 511 completed."},{"cite":"European Medicines Agency. European Medicines Agency recommends limiting long-term use of calcitonin medicines (press release, 20 July 2012).","where":"EMA","url":"https://www.ema.europa.eu/en/news/european-medicines-agency-recommends-limiting-long-term-use-calcitonin-medicines","note":"Withdrawal of the nasal spray; cancer signal from pooled trials."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade A on certainty; small, inconsistent osteoporosis effect and the 2012 withdrawal recorded."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"desmopressin","name":"Desmopressin","aliases":["DDAVP","Minirin","Nocdurna","Noctiva","1-deamino-8-D-arginine vasopressin"],"url":"https://lyoresearch.com/compounds/desmopressin","class":{"id":"endocrine-medicines","name":"Bone and endocrine peptide medicines","url":"https://lyoresearch.com/classes/endocrine-medicines"},"summary":"Desmopressin is a synthetic analogue of the antidiuretic hormone vasopressin that concentrates urine without raising blood pressure. It is approved for diabetes insipidus, bedwetting, nocturia and some bleeding disorders. A Cochrane review of 14 trials found it reduces night-time voids by a little under one per night in men. Its serious risk is hyponatraemia — low blood sodium — in about 7.6% of older adults, which is why sodium is monitored. It is on WADA's list as a masking agent.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"Cochrane review (14 RCTs, n=2,966) + decades of use","regulatory_status":"Approved (Rx)","molecule":{"formula":"C46H64N14O12S2","molecular_weight":"1069.2","cas":"16679-58-6","pubchem_cid":5311065,"note":null},"pharmacokinetics":{"basis":"label","route":"Intravenous or subcutaneous injection; also tablets, melt tablets and nasal spray","half_life":"About 2.8 hours","licensed_regimen":"Haemophilia A / von Willebrand type 1: 0.3 mcg/kg (max 20 mcg) IV over 15-30 min; central diabetes insipidus: 2-4 mcg daily in 1-2 divided doses SC or IV","product":"DDAVP injection","source":{"title":"DDAVP injection prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=651f6fee-a2c7-431b-8d5d-58b156c72244"}},"outcomes":[{"outcome":"Nocturia (night-time voids)","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":false,"human_studies":"Cochrane review, 14 RCTs (n=2,966 men)","evidence":"About 0.85 fewer voids per night at three to twelve months against placebo, with low-quality evidence; little difference at under three months. A separate meta-analysis in women found 0.41 fewer.","references":[{"citation":"Han J, Jung JH, Bakker CJ, Ebell MH, Dahm P. Desmopressin for treating nocturia in men.","where":"Cochrane Database Syst Rev, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/29055129/"},{"citation":"Cai X, et al. Efficacy and safety of desmopressin in women with nocturia: a systematic review and meta-analysis of randomized controlled trials.","where":"Int Urol Nephrol, 2019","url":"https://pubmed.ncbi.nlm.nih.gov/31352583/"}],"verbatim":{"text":"For intermediate-term follow-up (three to 12 months), desmopressin may reduce the number of nocturnal voids in an appreciable number of participants (MD -0.85, 95% CI -1.17 to -0.53; low-quality evidence).","citation":"Han J, Jung JH, Bakker CJ, Ebell MH, Dahm P. Desmopressin for treating nocturia in men.","url":"https://pubmed.ncbi.nlm.nih.gov/29055129/"}},{"outcome":"Hyponatraemia (older adults)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"Meta-analysis, 7 studies","evidence":"Pooled incidence of low sodium 7.6% in older adults treated for nocturia — the reason for sodium checks before and during treatment and for the boxed warning on the US nasal product.","references":[{"citation":"Weatherall M. The risk of hyponatremia in older adults using desmopressin for nocturia: a systematic review and meta-analysis.","where":"Neurourol Urodyn, 2004","url":"https://pubmed.ncbi.nlm.nih.gov/15227644/"}],"verbatim":{"text":"The pooled estimate for the incidence of hyponatremia was 7.6% (95% CI 3.7-15.1).","citation":"Weatherall M. The risk of hyponatremia in older adults using desmopressin for nocturia: a systematic review and meta-analysis.","url":"https://pubmed.ncbi.nlm.nih.gov/15227644/"}},{"outcome":"Central diabetes insipidus","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"Decades of use; the original indication","evidence":"Replaces the missing hormone; the standard treatment since the 1970s. Older trials, not modern RCTs, but the effect is unambiguous.","references":[{"citation":"Hahn D, et al. Desmopressin for nocturnal enuresis in children.","where":"Cochrane Database Syst Rev, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40728007/"}]},{"outcome":"Nocturnal enuresis in children","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"Cochrane review (2025 update)","evidence":"Reduces wet nights during treatment; relapse on stopping is common, and alarm training has more durable effect.","references":[{"citation":"Hahn D, et al. Desmopressin for nocturnal enuresis in children.","where":"Cochrane Database Syst Rev, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40728007/"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Nationally authorised products (Minirin, Nocdurna and generics) across member states."},{"region":"United States","status":"Approved, prescription-only","note":"DDAVP and generics; Nocdurna (2018) and Noctiva nasal spray (2017) for nocturia, the latter with a boxed warning for hyponatraemia."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Licensed for diabetes insipidus, enuresis, nocturia and haemophilia A / von Willebrand disease."},{"region":"Australia","status":"Registered, Schedule 4","note":"Minirin and generics on the ARTG."},{"region":"Canada","status":"Authorised, prescription-only","note":"DDAVP and generics."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Listed under S5 (diuretics and masking agents) since 2011, because it dilutes urine and can mask other substances."}],"faq":[{"q":"Is desmopressin a peptide?","a":"Yes — nine amino acids in a disulfide ring, a modified copy of the hormone vasopressin."},{"q":"Why is desmopressin banned in sport?","a":"It concentrates urine and lets an athlete drink to dilute a sample, which can hide other substances. WADA lists it as a masking agent, not for any performance effect."},{"q":"What is the main risk?","a":"Low blood sodium. In older adults treated for nocturia the pooled rate is about 7.6%; severe cases cause confusion and seizures. Sodium is checked before treatment and again after starting."}],"references":[{"cite":"Han J, Jung JH, Bakker CJ, Ebell MH, Dahm P. Desmopressin for treating nocturia in men.","where":"Cochrane Database Syst Rev, 2017","url":"https://pubmed.ncbi.nlm.nih.gov/29055129/","note":"14 studies, 2,966 men."},{"cite":"Cai X, et al. Efficacy and safety of desmopressin in women with nocturia: a systematic review and meta-analysis of randomized controlled trials.","where":"Int Urol Nephrol, 2019","url":"https://pubmed.ncbi.nlm.nih.gov/31352583/","note":"7 trials."},{"cite":"Weatherall M. The risk of hyponatremia in older adults using desmopressin for nocturia: a systematic review and meta-analysis.","where":"Neurourol Urodyn, 2004","url":"https://pubmed.ncbi.nlm.nih.gov/15227644/","note":"Pooled incidence 7.6%."},{"cite":"Hahn D, et al. Desmopressin for nocturnal enuresis in children.","where":"Cochrane Database Syst Rev, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40728007/"}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade A; small nocturia effect, hyponatraemia quantified, WADA S5 status recorded."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"thymalin","name":"Thymalin","aliases":["thymus extract peptides","Khavinson thymic bioregulator","Thymalin bioregulator"],"url":"https://lyoresearch.com/compounds/thymalin","class":{"id":"immune-peptides","name":"Immune, antimicrobial and repair-signal peptides","url":"https://lyoresearch.com/classes/immune-peptides"},"summary":"Thymalin is a mixture of short peptides extracted from calf thymus, developed in Soviet-era St Petersburg and sold as an immune 'bioregulator'. The evidence behind its anti-ageing reputation is a 2003 report of 266 elderly people followed for six to eight years, which claims halved mortality but describes neither randomisation nor blinding. No trial outside that group's institute exists in the indexed literature. It is not approved in any region this site covers.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"1 uncontrolled long-term series (n=266); Russian reports","regulatory_status":"Not approved (Russia only)","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"An undefined calf-thymus peptide extract — no molecular identity"},"pharmacokinetics":{"basis":"none","route":"Intramuscular as sold","half_life":"No human pharmacokinetic data (an extract, not a defined molecule)","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Mortality in the elderly","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"1 long-term series (n=266, 6–8 yr)","evidence":"Khavinson and Morozov report 2.0–2.1-fold lower mortality in thymalin-treated participants against a control group, and 4.1-fold with annual thymalin plus epithalamin. The abstract does not describe how participants were allocated or whether anyone was blinded; the same authors developed the products.","references":[{"citation":"Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life.","where":"Neuro Endocrinol Lett, 2003;24:233–240","url":"https://pubmed.ncbi.nlm.nih.gov/14523363/"}],"verbatim":{"text":"Such a significant improvement in the health state of the peptide-treated patients correlated with decreased mortality rate during observation: 2.0-2.1-fold in the Thymalin-treated group; 1.6-1.8-fold in the Epithalamin-treated group; 2.5-fold in the patients treated with Thymalin plus Epithalamin as compared to the control.","citation":"Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life.","url":"https://pubmed.ncbi.nlm.nih.gov/14523363/"}},{"outcome":"Respiratory infections","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"Same series","evidence":"A 2.0–2.4-fold fall in acute respiratory disease is reported in the same paper, with the same design limits.","references":[{"citation":"Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life.","where":"Neuro Endocrinol Lett, 2003;24:233–240","url":"https://pubmed.ncbi.nlm.nih.gov/14523363/"}]},{"outcome":"Independent replication","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":false,"human_studies":"None found","evidence":"LYO's search found no randomised trial of thymalin by any group outside the St Petersburg Institute of Bioregulation and Gerontology.","references":[{"citation":"PubMed search: thymalin randomized controlled trial — no independent RCT identified.","where":"PubMed, searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=thymalin+randomized"}]}],"regions":[{"region":"European Union","status":"Not authorised","note":"No marketing authorisation; supply for human use is unlawful."},{"region":"United States","status":"Not approved","note":"Not FDA-approved; not on any compounding list."},{"region":"United Kingdom","status":"Not licensed","note":"Unlicensed medicine."},{"region":"Australia","status":"Not on the ARTG","note":"Not registered."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved by any regulator WADA recognises, so S0 (non-approved substances)."}],"faq":[{"q":"Does thymalin extend life?","a":"One uncontrolled Russian series says so. Nothing else does. Without randomisation, healthier people may simply have been the ones treated."},{"q":"Is thymalin the same as thymosin alpha-1?","a":"No. Thymosin α1 is a defined 28-amino-acid peptide with twenty-plus randomised trials. Thymalin is an undefined extract with none."},{"q":"Is thymalin legal?","a":"It is registered in Russia. It has no authorisation in the EU, US, UK, Australia or Canada, and is banned in sport."}],"references":[{"cite":"Khavinson VKh, Morozov VG. Peptides of pineal gland and thymus prolong human life.","where":"Neuro Endocrinol Lett, 2003;24:233–240","url":"https://pubmed.ncbi.nlm.nih.gov/14523363/","note":"266 elderly participants, 6–8 years. No randomisation or blinding described."},{"cite":"PubMed search: thymalin randomized controlled trial — no independent RCT identified.","where":"PubMed, searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=thymalin+randomized"}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade C on the single uncontrolled series."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"pinealon","name":"Pinealon","aliases":["Glu-Asp-Arg","EDR peptide","pineal bioregulator tripeptide"],"url":"https://lyoresearch.com/compounds/pinealon","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"Pinealon is the tripeptide Glu-Asp-Arg, a synthetic 'bioregulator' from the St Petersburg group behind epitalon, sold for brain ageing and stress. Its indexed evidence is cell culture — it reduced free radicals and cell death in vitro — and rat experiments in hypoxia. The human reports are Russian-language, without controls and without indexed abstracts. No randomised trial exists. It is not approved anywhere this site covers.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0 controlled","regulatory_status":"Not approved","molecule":{"formula":"C15H26N6O8","molecular_weight":"418.40","cas":"175175-23-2","pubchem_cid":10273502,"note":"Recorded as Glu-Asp-Arg"},"pharmacokinetics":{"basis":"none","route":"Oral or injected as sold","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Cognition or brain ageing (human)","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0 controlled; Russian reports without abstracts","evidence":"Two Russian-language clinical reports (2012, 2015) are indexed by title only and describe uncontrolled use. LYO could not read a method or a result.","references":[{"citation":"PubMed search: pinealon — 22 results; human reports Russian-language without indexed abstracts (Meshchaninov 2015; Nazimko 2012).","where":"PubMed, searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=pinealon"}]},{"outcome":"Cell viability under oxidative stress (in vitro)","grade":"D","grade_meaning":"no human evidence","effect_size":"moderate","adverse":false,"human_studies":"Cell culture only","evidence":"Khavinson's 2011 study reports lower free-radical levels and less necrotic death in cultured cells — the origin of the neuroprotection claim.","references":[{"citation":"Khavinson V, et al. Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes.","where":"Rejuvenation Res, 2011","url":"https://pubmed.ncbi.nlm.nih.gov/21978084/"}]},{"outcome":"Hypoxia tolerance (rats)","grade":"D","grade_meaning":"no human evidence","effect_size":"small","adverse":false,"human_studies":"Animal only","evidence":"Aged rats given pinealon before hypoxia showed behavioural and caspase-3 changes in several small studies from the same institute.","references":[{"citation":"PubMed search: pinealon — 22 results; human reports Russian-language without indexed abstracts (Meshchaninov 2015; Nazimko 2012).","where":"PubMed, searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=pinealon"}]}],"regions":[{"region":"European Union","status":"Not authorised","note":"No marketing authorisation."},{"region":"United States","status":"Not approved","note":"Not FDA-approved."},{"region":"United Kingdom","status":"Not licensed","note":"Unlicensed."},{"region":"Australia","status":"Not on the ARTG","note":"Not registered."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved, so S0 (non-approved substances)."}],"faq":[{"q":"Does pinealon work?","a":"There is no controlled human evidence either way. The indexed studies are in cells and rats."},{"q":"Is pinealon the same as epitalon?","a":"No. Epitalon is a four-residue pineal peptide with a telomerase story; pinealon is a three-residue 'brain' peptide from the same developers. Neither has a randomised trial."}],"references":[{"cite":"PubMed search: pinealon — 22 results; human reports Russian-language without indexed abstracts (Meshchaninov 2015; Nazimko 2012).","where":"PubMed, searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=pinealon"},{"cite":"Khavinson V, et al. Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes.","where":"Rejuvenation Res, 2011","url":"https://pubmed.ncbi.nlm.nih.gov/21978084/","note":"Cell culture."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade D: no controlled human study."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"foxo4-dri","name":"FOXO4-DRI","aliases":["FOXO4 D-retro-inverso peptide","senolytic peptide","Proxofim"],"url":"https://lyoresearch.com/compounds/foxo4-dri","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"FOXO4-DRI is a cell-penetrating peptide designed to pry the protein FOXO4 away from p53 inside senescent cells, causing those cells to die. In a 2017 Cell paper it restored fitness, fur density and kidney function in aged and prematurely ageing mice. That is the entire evidence base: no human trial, no human safety data, and no regulatory filing. Products sold under the name are unlicensed research chemicals.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0","regulatory_status":"Not approved (preclinical)","molecule":{"formula":"C228H388N86O64","molecular_weight":"5358","cas":"2460055-10-9","pubchem_cid":167312269,"note":"Record is the TFA salt form"},"pharmacokinetics":{"basis":"none","route":"Injected as sold; no human study","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Any outcome in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0","evidence":"No clinical study is registered or published. LYO's search found none.","references":[{"citation":"PubMed and ClinicalTrials.gov search: FOXO4-DRI — no human study identified.","where":"Searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=FOXO4-DRI+clinical"}]},{"outcome":"Fitness, fur density and renal function (aged mice)","grade":"D","grade_meaning":"no human evidence","effect_size":"large","adverse":false,"human_studies":"Animal only","evidence":"Baar and colleagues report selective clearance of senescent cells and functional restoration in fast-ageing and naturally aged mice, and protection against chemotherapy toxicity.","references":[{"citation":"Baar MP, Brandt RMC, Putavet DA, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging.","where":"Cell, 2017;169:132–147","url":"https://pubmed.ncbi.nlm.nih.gov/28340339/"}]},{"outcome":"Senescent cell clearance (human cells in vitro)","grade":"D","grade_meaning":"no human evidence","effect_size":"moderate","adverse":false,"human_studies":"Cell culture","evidence":"Removed senescent cells from expanded human chondrocytes in a 2021 study — the closest the compound has come to a human tissue.","references":[{"citation":"Senolytic peptide FOXO4-DRI selectively removes senescent cells from in vitro expanded human chondrocytes.","where":"Front Bioeng Biotechnol, 2021","url":"https://pubmed.ncbi.nlm.nih.gov/33996787/"}]}],"regions":[{"region":"European Union","status":"Not authorised","note":"Preclinical; supply for human use is unlawful."},{"region":"United States","status":"Not approved","note":"Not FDA-approved; no IND announced."},{"region":"United Kingdom","status":"Not licensed","note":"Unlicensed."},{"region":"Australia","status":"Not on the ARTG","note":"Not registered."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved, so S0 (non-approved substances)."}],"faq":[{"q":"Has FOXO4-DRI been tested in humans?","a":"No. Not one trial, at any phase. The evidence is mice and cell culture."},{"q":"Is FOXO4-DRI a senolytic?","a":"In mice, yes — it selectively killed senescent cells. Whether it does so safely in people is unknown."},{"q":"Why is it sold if untested?","a":"Because the mouse paper was widely reported and the sequence is public. Availability online says nothing about safety or legality; it is an unapproved substance everywhere."}],"references":[{"cite":"Baar MP, Brandt RMC, Putavet DA, et al. Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging.","where":"Cell, 2017;169:132–147","url":"https://pubmed.ncbi.nlm.nih.gov/28340339/","note":"Mice."},{"cite":"PubMed and ClinicalTrials.gov search: FOXO4-DRI — no human study identified.","where":"Searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=FOXO4-DRI+clinical"},{"cite":"Senolytic peptide FOXO4-DRI selectively removes senescent cells from in vitro expanded human chondrocytes.","where":"Front Bioeng Biotechnol, 2021","url":"https://pubmed.ncbi.nlm.nih.gov/33996787/","note":"Human cells in culture."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade D: no human study."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"petrelintide","name":"Petrelintide","aliases":["ZP8396","long-acting amylin analogue","Zealand/Roche amylin"],"url":"https://lyoresearch.com/compounds/petrelintide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Petrelintide is a once-weekly amylin receptor agonist developed by Zealand Pharma and partnered with Roche. In ZUPREME-1, a 493-person phase 2 trial published in September 2026, adults with obesity and no diabetes lost 7.9–9.8% of body weight at 28 weeks against 1.7% on placebo, and up to 10.7% by week 42. Nausea affected 20% against 6% on placebo; vomiting and diarrhoea were no more common than on placebo. A phase 3 programme of about 7,000 people began in September 2026. It is not approved anywhere.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"1 phase 2 RCT (n=493) and 2 phase 1 RCTs published; phase 3 running","regulatory_status":"Investigational (phase 3)","molecule":{"formula":"C185H305N49O61","molecular_weight":"4192","cas":null,"pubchem_cid":172915807,"note":"No CAS number listed on the PubChem record"},"pharmacokinetics":{"basis":"human","route":"Subcutaneous, once weekly","half_life":"About 10 days (phase 1)","licensed_regimen":null,"product":null,"source":{"title":"Olsen MB, et al. Petrelintide phase 1 trials. Diabetes Obes Metab 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42017294/"}},"outcomes":[{"outcome":"Body weight","grade":"C","grade_meaning":"weak human evidence","effect_size":"moderate","adverse":false,"human_studies":"1 phase 2 RCT (n=493, 42 wk); phase 1","evidence":"ZUPREME-1, published in The Lancet Diabetes & Endocrinology on 29 September 2026: 493 adults with obesity, or overweight with hypertension or dyslipidaemia, and no type 2 diabetes were randomised 5:1 to one of five weekly doses or placebo. At 28 weeks, the primary endpoint, weight had fallen 7.9–9.8% against 1.7% on placebo; by week 42 the largest loss was 10.7%. Efficacy estimand, so participants who stopped are not fully counted. The earlier phase 1 trial saw up to 8.6% at 16 weeks and measured a half-life of about ten days.","references":[{"citation":"Garvey WT, et al. Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial.","where":"Lancet Diabetes Endocrinol, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42810355/"},{"citation":"Olsen MB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of petrelintide for weight management: two randomized, controlled phase 1 trials.","where":"Diabetes Obes Metab, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42017294/"}],"verbatim":{"text":"Mean percentage change in bodyweight from baseline after 28 weeks (efficacy estimand) was -7·9% (95% CI -9·0 to -6·7) with petrelintide 1·0 mg, -7·9% (-9·0 to -6·7) with petrelintide 2·5 mg, -9·8% (-10·9 to -8·6) with petrelintide 5·0 mg, -9·3% (-10·5 to -8·2) with petrelintide 7·0 mg, and -9·4% (-10·5 to -8·3) with petrelintide 9·0 mg versus -1·7% (-2·8 to -0·5) with placebo.","citation":"Garvey WT, et al. Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/42810355/"}},{"outcome":"GI side effects","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":true,"human_studies":"1 phase 2 RCT (n=485 dosed); phase 1","evidence":"ZUPREME-1: nausea in 20% against 6% on placebo, described as predominantly mild and during dose escalation; vomiting 3% vs 6%, diarrhoea 7% vs 7%, constipation 7% vs 4%. No deaths. In the earlier phase 1 trial nausea occurred in 17–33% against 17% on placebo, and one participant stopped for gut symptoms. Whether the profile holds over 64 weeks in phase 3 is the open question.","references":[{"citation":"Garvey WT, et al. Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial.","where":"Lancet Diabetes Endocrinol, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42810355/"},{"citation":"Olsen MB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of petrelintide for weight management: two randomized, controlled phase 1 trials.","where":"Diabetes Obes Metab, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42017294/"}],"verbatim":{"text":"The most common adverse event with petrelintide was nausea (79 [20%] of 404 participants vs five [6%] participants with placebo).","citation":"Garvey WT, et al. Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial.","url":"https://pubmed.ncbi.nlm.nih.gov/42810355/"}}],"regions":[{"region":"European Union","status":"Not authorised","note":"Investigational."},{"region":"United States","status":"Not approved","note":"Investigational; phase 3 running since September 2026. Products sold under the name are not the trial drug."},{"region":"United Kingdom","status":"Not licensed","note":"No MHRA licence."},{"region":"Australia","status":"Not on the ARTG","note":"Investigational only."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved anywhere, so S0 (non-approved substances)."}],"faq":[{"q":"How much weight do people lose on petrelintide?","a":"7.9–9.8% at 28 weeks across five doses in the published phase 2 trial, against 1.7% on placebo, and up to 10.7% by week 42. Those figures come from one dose-finding trial; phase 3 will give the 64-week number."},{"q":"Is petrelintide better tolerated than semaglutide?","a":"In its phase 2 trial nausea affected 20% of participants and vomiting 3%, with diarrhoea no more common than on placebo. No trial has compared it directly with semaglutide, and the weight loss was smaller too. Treat the tolerability advantage as a hypothesis that phase 3 has to confirm."}],"references":[{"cite":"Olsen MB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of petrelintide for weight management: two randomized, controlled phase 1 trials.","where":"Diabetes Obes Metab, 2026","url":"https://pubmed.ncbi.nlm.nih.gov/42017294/","note":"Single- and multiple-ascending-dose trials; 16-week part in adults with overweight or obesity."},{"cite":"Genentech / Zealand Pharma. Positive phase II results for petrelintide (ZUPREME-1).","where":"Press release, 5 Mar 2026","url":"https://www.businesswire.com/news/home/20260305198579/en/Genentech-Announces-Positive-Phase-II-Results-for-Petrelintide-an-Amylin-Analog-Developed-for-People-Living-With-Overweight-and-Obesity","note":"Topline only; not peer-reviewed."},{"cite":"Garvey WT, et al. Petrelintide, a human amylin analogue for the treatment of obesity (ZUPREME 1): a randomised, double-blind, placebo-controlled, phase 2 trial.","where":"Lancet Diabetes Endocrinol, 2026 (online 29 Sep)","url":"https://pubmed.ncbi.nlm.nih.gov/42810355/","note":"493 randomised, 485 dosed; 32 sites in Poland, Romania and the USA; 42 weeks, primary endpoint at 28 weeks. NCT06662539."},{"cite":"Zealand Pharma. Initiation of the registrational phase 3 ZUPREME programme of petrelintide in people with overweight or obesity.","where":"Press release No. 17/2026, 22 Sep 2026","url":"https://www.globenewswire.com/news-release/2026/09/22/3366613/0/en/zealand-pharma-announces-initiation-of-the-registrational-phase-3-zupreme-program-of-petrelintide-in-people-with-overweight-or-obesity.html","note":"ZUPREME-3, -4 and -5; about 7,000 participants; primary endpoint percentage change in body weight at week 64."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"ZUPREME-1 phase 2 published (Lancet Diabetes Endocrinol, 29 Sep 2026): weight and side-effect rows now rest on the paper, with new verbatim results replacing the phase 1 sentences; phase 3 start (22 Sep 2026) recorded. Grade held at C for stage."},{"date":"2026-09-23","note":"Initial publication from the phase 1 paper. Grade C for stage."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"lixisenatide","name":"Lixisenatide","aliases":["Adlyxin","Lyxumia","AVE0010","Soliqua (with insulin glargine)"],"url":"https://lyoresearch.com/compounds/lixisenatide","class":{"id":"glp-1-agonists","name":"GLP-1 and incretin agonists","url":"https://lyoresearch.com/classes/glp-1-agonists"},"summary":"Lixisenatide is a short-acting GLP-1 receptor agonist derived from exendin-4, approved for type 2 diabetes since 2013 and now sold mainly in combination with insulin glargine. Its cardiovascular-outcomes trial in 6,068 people after a heart attack was neutral. In 2024 a French phase 2 trial found that a year of lixisenatide slowed motor progression in early Parkinson's disease by about three points on the standard scale, with nausea in nearly half. It is prescription-only; the standalone product has been withdrawn in some markets.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"GetGoal programme; ELIXA (n=6,068); LIXIPARK (n=156)","regulatory_status":"Approved (Rx)","molecule":{"formula":"C215H347N61O65S","molecular_weight":"4858","cas":"320367-13-3","pubchem_cid":90472060,"note":null},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection, once daily before the first meal","half_life":"About 3 hours","licensed_regimen":"Soliqua: 15–60 units of insulin glargine with 5–20 mcg lixisenatide once daily, titrated to glucose; standalone lixisenatide (Adlyxin) was 10 mcg daily for 14 days then 20 mcg daily","product":"Soliqua 100/33 (with insulin glargine)","source":{"title":"Soliqua 100/33 prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4bba538b-cf7c-4310-ae8f-cb711ed21bcc"}},"outcomes":[{"outcome":"Blood glucose (HbA1c)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"GetGoal programme (10+ RCTs)","evidence":"Approval-grade HbA1c reductions as an add-on in type 2 diabetes, with a particular effect on post-meal glucose because of its short action.","references":[{"citation":"Soliqua 100/33 prescribing information (insulin glargine and lixisenatide).","where":"DailyMed","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4bba538b-cf7c-4310-ae8f-cb711ed21bcc"}]},{"outcome":"Major cardiovascular events","grade":"A","grade_meaning":"established in humans","effect_size":"not measurable","adverse":false,"human_studies":"1 large RCT (ELIXA, n=6,068)","evidence":"In people with type 2 diabetes and a recent acute coronary syndrome, lixisenatide neither increased nor reduced major cardiovascular events — non-inferior to placebo, not superior. The first GLP-1 outcomes trial, and a neutral one.","references":[{"citation":"Pfeffer MA, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome (ELIXA).","where":"N Engl J Med, 2015;373:2247–2257","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Pfeffer+lixisenatide+acute+coronary+syndrome+ELIXA+2015"}],"verbatim":{"text":"A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (P<0.001) but did not show superiority (P=0.81).","citation":"Pfeffer MA, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome (ELIXA).","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Pfeffer+lixisenatide+acute+coronary+syndrome+ELIXA+2015"}},{"outcome":"Motor progression in early Parkinson's disease","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":false,"human_studies":"1 phase 2 RCT (n=156, 12 mo)","evidence":"LIXIPARK: motor scores were essentially unchanged on lixisenatide and worsened by three points on placebo over a year — a statistically clear but clinically modest difference, in a trial too small and short to establish disease modification.","references":[{"citation":"Meissner WG, et al. Trial of lixisenatide in early Parkinson's disease (LIXIPARK).","where":"N Engl J Med, 2024;390:1176–1185","url":"https://pubmed.ncbi.nlm.nih.gov/38598572/"}],"verbatim":{"text":"At 12 months, scores on the MDS-UPDRS part III had changed by -0.04 points (indicating improvement) in the lixisenatide group and 3.04 points (indicating worsening disability) in the placebo group (difference, 3.08; 95% confidence interval, 0.86 to 5.30; P = 0.007).","citation":"Meissner WG, et al. Trial of lixisenatide in early Parkinson's disease (LIXIPARK).","url":"https://pubmed.ncbi.nlm.nih.gov/38598572/"}},{"outcome":"GI side effects","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":true,"human_studies":"All trials","evidence":"The class profile; in the Parkinson's trial, where participants were not diabetic, nausea affected almost half.","references":[{"citation":"Meissner WG, et al. Trial of lixisenatide in early Parkinson's disease (LIXIPARK).","where":"N Engl J Med, 2024;390:1176–1185","url":"https://pubmed.ncbi.nlm.nih.gov/38598572/"}],"verbatim":{"text":"Nausea occurred in 46% of participants receiving lixisenatide, and vomiting occurred in 13%.","citation":"Meissner WG, et al. Trial of lixisenatide in early Parkinson's disease (LIXIPARK).","url":"https://pubmed.ncbi.nlm.nih.gov/38598572/"}}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Lyxumia authorised 2013; Suliqua (with insulin glargine) authorised 2017. Check availability of the standalone product, which Sanofi has discontinued in several markets."},{"region":"United States","status":"Approved, prescription-only","note":"Adlyxin approved 2016; only the Soliqua combination is currently listed on DailyMed, the standalone product having been discontinued."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"Lyxumia and Suliqua licensed by the MHRA."},{"region":"Australia","status":"Registered, Schedule 4","note":"Registered as Lyxumia / Soliqua."},{"region":"Canada","status":"Authorised, prescription-only","note":"Adlyxine and Soliqua."},{"region":"Sport (WADA)","status":"Not prohibited","note":"GLP-1 receptor agonists are not on the Prohibited List."}],"faq":[{"q":"Does lixisenatide treat Parkinson's disease?","a":"One phase 2 trial found slower motor decline over a year. That is promising and not proof; it is not approved for Parkinson's, and larger trials are needed."},{"q":"Why is lixisenatide less used than semaglutide?","a":"It is short-acting and once-daily, produces less weight loss, and its heart trial was neutral where semaglutide's was positive."},{"q":"Is lixisenatide a peptide?","a":"Yes — a 44-amino-acid analogue of exendin-4, the same lizard-venom peptide exenatide copies."}],"references":[{"cite":"Pfeffer MA, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome (ELIXA).","where":"N Engl J Med, 2015;373:2247–2257","url":"https://pubmed.ncbi.nlm.nih.gov/?term=Pfeffer+lixisenatide+acute+coronary+syndrome+ELIXA+2015","note":"6,068 randomised; HR 1.02."},{"cite":"Meissner WG, et al. Trial of lixisenatide in early Parkinson's disease (LIXIPARK).","where":"N Engl J Med, 2024;390:1176–1185","url":"https://pubmed.ncbi.nlm.nih.gov/38598572/","note":"156 randomised, 12 months. NCT03439943."},{"cite":"Soliqua 100/33 prescribing information (insulin glargine and lixisenatide).","where":"DailyMed","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4bba538b-cf7c-4310-ae8f-cb711ed21bcc","note":"Regulatory status and pharmacokinetics."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade A on the approval programme and ELIXA; Parkinson's row at B."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"insulin","name":"Insulin","aliases":["insulin human","Humulin","Novolin","insulin analogues (lispro, aspart, glargine, detemir, degludec)"],"url":"https://lyoresearch.com/compounds/insulin","class":{"id":"endocrine-medicines","name":"Bone and endocrine peptide medicines","url":"https://lyoresearch.com/classes/endocrine-medicines"},"summary":"Insulin is the 51-amino-acid hormone that lets cells take up glucose; recombinant human insulin and its engineered analogues are the treatment for type 1 diabetes and a mainstay of type 2. The landmark trials are settled: intensive insulin therapy cut new diabetic eye disease by 76% over six and a half years in the DCCT, and intensive glucose control reduced microvascular complications by a quarter over ten years in UKPDS. The cost, quantified in the same trials, is severe hypoglycaemia. It is on this site as the reference peptide, and because it is on WADA's list.","overall_grade":"A","overall_grade_meaning":"established in humans","human_trials":"DCCT (n=1,441), UKPDS (n=3,867) and a century of use","regulatory_status":"Approved (Rx)","molecule":{"formula":"C257H383N65O77S6","molecular_weight":"5808","cas":"11061-68-0","pubchem_cid":118984375,"note":"Human insulin; the analogues differ by a few residues"},"pharmacokinetics":{"basis":"label","route":"Subcutaneous injection; intravenous infusion in hospital","half_life":"About 1.5 hours after subcutaneous injection (range 40 minutes to 7 hours); about 20 minutes intravenous","licensed_regimen":"Individualised to the person's metabolic needs, blood glucose monitoring and glycaemic goals; regular insulin is generally used with an intermediate- or long-acting insulin","product":"Humulin R (insulin human)","source":{"title":"Humulin R prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b519bd83-038c-4ec5-a231-a51ec5cc291f"}},"outcomes":[{"outcome":"Diabetic retinopathy (type 1, intensive vs conventional)","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":false,"human_studies":"1 large RCT (DCCT, n=1,441, 6.5 yr)","evidence":"Intensive insulin therapy — pump or three or more daily injections with frequent glucose monitoring — reduced new retinopathy by 76% and slowed existing retinopathy by 54%. Kidney and nerve complications fell too.","references":[{"citation":"The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.","where":"N Engl J Med, 1993;329:977–986","url":"https://pubmed.ncbi.nlm.nih.gov/8366922/"}],"verbatim":{"text":"In the primary-prevention cohort, intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent (95 percent confidence interval, 62 to 85 percent), as compared with conventional therapy.","citation":"The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.","url":"https://pubmed.ncbi.nlm.nih.gov/8366922/"}},{"outcome":"Microvascular complications (type 2)","grade":"A","grade_meaning":"established in humans","effect_size":"moderate","adverse":false,"human_studies":"1 large RCT (UKPDS 33, n=3,867, 10 yr)","evidence":"Intensive glucose control with insulin or a sulphonylurea cut microvascular endpoints by 25% over ten years in newly diagnosed type 2 diabetes; the effect on heart attacks and deaths did not reach significance in the main trial, though it emerged in the ten-year follow-up.","references":[{"citation":"UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).","where":"Lancet, 1998;352:837–853","url":"https://pubmed.ncbi.nlm.nih.gov/9742976/"}],"verbatim":{"text":"Most of the risk reduction in the any diabetes-related aggregate endpoint was due to a 25% risk reduction (7-40, p=0.0099) in microvascular endpoints, including the need for retinal photocoagulation.","citation":"UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).","url":"https://pubmed.ncbi.nlm.nih.gov/9742976/"}},{"outcome":"Severe hypoglycaemia","grade":"A","grade_meaning":"established in humans","effect_size":"large","adverse":true,"human_studies":"Both landmark RCTs","evidence":"The defining harm. Intensive therapy in the DCCT roughly tripled severe hypoglycaemia; in UKPDS the rate of major episodes on insulin was 1.8% a year against 0.7% on conventional treatment.","references":[{"citation":"The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.","where":"N Engl J Med, 1993;329:977–986","url":"https://pubmed.ncbi.nlm.nih.gov/8366922/"},{"citation":"UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).","where":"Lancet, 1998;352:837–853","url":"https://pubmed.ncbi.nlm.nih.gov/9742976/"}],"verbatim":{"text":"The chief adverse event associated with intensive therapy was a two-to-threefold increase in severe hypoglycemia.","citation":"The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.","url":"https://pubmed.ncbi.nlm.nih.gov/8366922/"}},{"outcome":"Weight gain","grade":"A","grade_meaning":"established in humans","effect_size":"small","adverse":true,"human_studies":"UKPDS and many","evidence":"Intensive treatment added about 2.9 kg over ten years in UKPDS — the reason insulin is the wrong tool for anyone seeking to lose weight and one reason the GLP-1 drugs exist.","references":[{"citation":"UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).","where":"Lancet, 1998;352:837–853","url":"https://pubmed.ncbi.nlm.nih.gov/9742976/"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Human insulins and analogues centrally authorised; some countries allow pharmacy sale of human insulin without prescription."},{"region":"United States","status":"Approved; some human insulins available without prescription","note":"Analogues are prescription-only. Human regular and NPH insulin (Humulin, Novolin) can be sold over the counter in most states. In 2026 the FDA approved two once-weekly basal insulins for adults with type 2 diabetes: Awiqli (insulin icodec) on 26 March and Onswik (insulin efsitora alfa) on 23 September."},{"region":"United Kingdom","status":"Licensed, prescription-only","note":"All insulins are prescription-only medicines."},{"region":"Australia","status":"Registered, Schedule 4","note":"Prescription-only; PBS-subsidised."},{"region":"Canada","status":"Authorised; human insulin available without prescription","note":"Human insulins are Schedule II (behind the counter, no prescription); analogues vary."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Insulins are listed under S4 (hormone and metabolic modulators), in and out of competition; a therapeutic use exemption is required for athletes with diabetes."}],"faq":[{"q":"Why is insulin on a peptide reference site?","a":"Because it is the original peptide medicine, the standard every other evidence page is measured against, and a compound misused outside medicine for muscle gain — which is why sport bans it."},{"q":"Is insulin a peptide?","a":"Yes — 51 amino acids in two chains, technically a small protein. It was the first protein sequenced (1951) and the first made by recombinant DNA (1982)."},{"q":"What is the main danger?","a":"Hypoglycaemia: too much insulin for the food eaten drops blood sugar to levels that cause confusion, seizures and death. Every landmark trial that improved outcomes with tighter control also increased severe hypoglycaemia."}],"references":[{"cite":"The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.","where":"N Engl J Med, 1993;329:977–986","url":"https://pubmed.ncbi.nlm.nih.gov/8366922/","note":"1,441 patients, mean 6.5 years."},{"cite":"UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).","where":"Lancet, 1998;352:837–853","url":"https://pubmed.ncbi.nlm.nih.gov/9742976/","note":"3,867 newly diagnosed patients, 10 years."},{"cite":"Humulin R (insulin human) prescribing information.","where":"DailyMed","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b519bd83-038c-4ec5-a231-a51ec5cc291f","note":"Pharmacokinetics and description."},{"cite":"FDA. Novel Drug Approvals for 2026 (Awiqli, insulin icodec-abae, 26 March 2026; Onswik, insulin efsitora alfa-gobe, 23 September 2026).","where":"FDA, read 7 Oct 2026","url":"https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026","note":"Both approved to improve glycaemic control in adults with type 2 diabetes."}],"last_reviewed":"2026-10-07","literature_searched_to":"2026-10-07","changelog":[{"date":"2026-10-07","note":"US row: the two once-weekly basal insulins approved by the FDA in 2026 (Awiqli, 26 March; Onswik, 23 September) added. Grades unchanged."},{"date":"2026-09-23","note":"Initial publication as the reference peptide. Grade A on DCCT and UKPDS."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"collagen-peptides","name":"Collagen peptides","aliases":["hydrolysed collagen","collagen hydrolysate","bioactive collagen peptides","collagen supplement"],"url":"https://lyoresearch.com/compounds/collagen-peptides","class":{"id":"supplement-peptides","name":"Peptides sold as supplements","url":"https://lyoresearch.com/classes/supplement-peptides"},"summary":"Collagen peptides are collagen broken down by enzymes into short chains that dissolve in water and are sold as powders for skin, joints and hair. Meta-analyses of the small trials find improved skin hydration and elasticity, but the 2025 analysis that separated trials by funding found the effect only in industry-funded and low-quality studies; independent, high-quality trials showed none. Joint-pain trials are similarly mixed. It is a food supplement, safe, and probably doing less than the label says.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"20+ small RCTs; meta-analyses disagree by funding and quality","regulatory_status":"Food supplement","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"A mixture of peptides of varying length from hydrolysed collagen — no single molecular identity"},"pharmacokinetics":{"basis":"none","route":"Oral (powder or capsules)","half_life":"Not applicable — a mixture digested to peptides and amino acids; no single half-life","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Skin hydration and elasticity","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"23–26 RCTs in meta-analyses (n≈1,500–1,700)","evidence":"Pooled across all trials the effect is positive; sorted by funding and quality, the independent and high-quality trials show no benefit. Two meta-analyses reach opposite conclusions on the same literature, which is itself the finding.","references":[{"citation":"Myung SK, et al. Effects of collagen supplements on skin aging: a systematic review and meta-analysis of randomized controlled trials.","where":"Am J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40324552/"},{"citation":"Pu SY, et al. Effects of oral collagen for skin anti-aging: a systematic review and meta-analysis.","where":"Nutrients, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37432180/"}],"verbatim":{"text":"However, in the subgroup meta-analysis by funding source, studies not receiving funding from pharmaceutical companies revealed no effect of collagen supplements for improving skin hydration, elasticity, and wrinkles, while those receiving funding from pharmaceutical companies did show significant effects.","citation":"Myung SK, et al. Effects of collagen supplements on skin aging: a systematic review and meta-analysis of randomized controlled trials.","url":"https://pubmed.ncbi.nlm.nih.gov/40324552/"}},{"outcome":"Joint pain and function","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"Several small RCTs; one 9-month trial (3 arms)","evidence":"A 9-month trial in active adults found improved daily-activity and pain scores on 10 g a day, but the pain effect appeared only in a subgroup of frequent exercisers. Other trials in knee osteoarthritis report small improvements; none is large.","references":[{"citation":"Kviatkovsky SA, et al. Collagen peptides supplementation improves function, pain, and physical and mental outcomes in active adults.","where":"J Int Soc Sports Nutr, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37551682/"}],"verbatim":{"text":"Improvements in ADLs (p = .031, ηp2 = .096) and pain (p = .037, ηp2 = .164) were observed with 10 g/d CP over 6 months, although pain only improved in high frequency exercisers (>180 min/week).","citation":"Kviatkovsky SA, et al. Collagen peptides supplementation improves function, pain, and physical and mental outcomes in active adults.","url":"https://pubmed.ncbi.nlm.nih.gov/37551682/"}},{"outcome":"Safety","grade":"B","grade_meaning":"probable, not settled","effect_size":"not measurable","adverse":true,"human_studies":"All trials","evidence":"No safety signal in any trial; it is digested like any dietary protein. The risk is to the wallet, not the body.","references":[{"citation":"Pu SY, et al. Effects of oral collagen for skin anti-aging: a systematic review and meta-analysis.","where":"Nutrients, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37432180/"}]}],"regions":[{"region":"European Union","status":"Food supplement","note":"Sold as food; no authorised health claim for skin or joints under the EU claims register."},{"region":"United States","status":"Dietary supplement","note":"Sold under DSHEA; structure/function claims only."},{"region":"United Kingdom","status":"Food supplement","note":"Food law; no authorised health claim."},{"region":"Australia","status":"Food or listed complementary medicine","note":"Depending on presentation."},{"region":"Canada","status":"Natural health product","note":"Licensed NPN products exist with limited claims."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the Prohibited List."}],"faq":[{"q":"Do collagen peptides work for skin?","a":"The pooled trials say a little; the independent, high-quality trials say no. The 2025 meta-analysis that made that split concluded there is no clinical evidence to support the use for skin ageing."},{"q":"Do collagen peptides help joints?","a":"Small trials report small improvements in pain and function, often in subgroups. Nothing large or independent settles it."},{"q":"Is it safe?","a":"Yes. It is a food protein; no trial has found a safety problem."}],"references":[{"cite":"Myung SK, et al. Effects of collagen supplements on skin aging: a systematic review and meta-analysis of randomized controlled trials.","where":"Am J Med, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40324552/","note":"23 RCTs, 1,474 participants; analysed by funding source and quality."},{"cite":"Pu SY, et al. Effects of oral collagen for skin anti-aging: a systematic review and meta-analysis.","where":"Nutrients, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37432180/","note":"26 RCTs, 1,721 participants; positive pooled effect, biases noted."},{"cite":"Kviatkovsky SA, et al. Collagen peptides supplementation improves function, pain, and physical and mental outcomes in active adults.","where":"J Int Soc Sports Nutr, 2023","url":"https://pubmed.ncbi.nlm.nih.gov/37551682/","note":"Three-arm RCT, 9 months."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade C: many small trials, effect dependent on funding and quality."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"carnosine","name":"Carnosine","aliases":["L-carnosine","beta-alanyl-L-histidine","β-alanine (precursor)"],"url":"https://lyoresearch.com/compounds/carnosine","class":{"id":"supplement-peptides","name":"Peptides sold as supplements","url":"https://lyoresearch.com/classes/supplement-peptides"},"summary":"Carnosine is a dipeptide of beta-alanine and histidine concentrated in muscle and brain, sold as a supplement for glucose control, ageing and exercise. A 2025 meta-analysis of eight randomised trials in 377 people with prediabetes or type 2 diabetes found modest reductions in fasting glucose and HbA1c against placebo, with no effect on weight or insulin resistance. The trials are small and short, and oral carnosine is largely broken down in blood before it reaches tissue. It is a food supplement, not a medicine.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"8 small RCTs (n=377) in a meta-analysis","regulatory_status":"Food supplement","molecule":{"formula":"C9H14N4O3","molecular_weight":"226.23","cas":"305-84-0","pubchem_cid":439224,"note":null},"pharmacokinetics":{"basis":"none","route":"Oral","half_life":"No half-life figure recorded by LYO; carnosine is hydrolysed in blood by serum carnosinase, which is why plasma levels are hard to sustain","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Blood glucose (fasting glucose and HbA1c) in prediabetes and type 2 diabetes","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"8 RCTs (n=377) pooled","evidence":"Standardised mean differences of about half a standard deviation for fasting glucose and a third for HbA1c against placebo. Trials of 12–14 weeks; several at high risk of bias.","references":[{"citation":"Li N, et al. Effect of carnosine or beta-alanine supplementation therapy for prediabetes or type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.","where":"BMC Endocr Disord, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40999397/"}],"verbatim":{"text":"Our analysis indicated that supplementation significantly reduced fasting blood glucose (FBG) (SMD: -0.53; 95% CI: -0.75 to -0.31; p < 0.00001) and hemoglobin A1c (HbA1c) levels (SMD:-0.36; 95% CI:-0.59 to -0.12; p = 0.003) compared to placebo.","citation":"Li N, et al. Effect of carnosine or beta-alanine supplementation therapy for prediabetes or type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.","url":"https://pubmed.ncbi.nlm.nih.gov/40999397/"}},{"outcome":"Body weight and insulin resistance","grade":"C","grade_meaning":"weak human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Same meta-analysis","evidence":"No effect on BMI, fasting insulin or HOMA-IR; a small fall in total cholesterol.","references":[{"citation":"Li N, et al. Effect of carnosine or beta-alanine supplementation therapy for prediabetes or type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.","where":"BMC Endocr Disord, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40999397/"}],"verbatim":{"text":"No significant effects were observed on body mass index (BMI), fasting insulin. low-density lipoprotein cholesterol (LDL-c) or high-density lipoprotein cholesterol (HDL-c), but a lowering effect was observed in total cholesterol (TC).","citation":"Li N, et al. Effect of carnosine or beta-alanine supplementation therapy for prediabetes or type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.","url":"https://pubmed.ncbi.nlm.nih.gov/40999397/"}},{"outcome":"Cognition or ageing","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"No adequate trial","evidence":"The anti-ageing use rests on animal and cell work on glycation and oxidative stress; no controlled human trial of an ageing endpoint exists.","references":[{"citation":"PubMed search: carnosine supplementation randomized trial cognition OR aging — no adequately powered trial of an ageing endpoint identified.","where":"PubMed, searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=carnosine+supplementation+randomized+cognition"}]}],"regions":[{"region":"European Union","status":"Food supplement","note":"Sold as food; no authorised health claim."},{"region":"United States","status":"Dietary supplement","note":"Sold under DSHEA."},{"region":"United Kingdom","status":"Food supplement","note":"Food law."},{"region":"Australia","status":"Listed complementary medicine or food","note":"Depending on presentation."},{"region":"Canada","status":"Natural health product","note":"NPN products exist."},{"region":"Sport (WADA)","status":"Not prohibited","note":"Not on the Prohibited List; beta-alanine is likewise permitted."}],"faq":[{"q":"Does carnosine lower blood sugar?","a":"Modestly, in eight small trials pooled together — about a third of a standard deviation in HbA1c. Not a treatment for diabetes; possibly a small adjunct, if larger trials agree."},{"q":"Is carnosine the same as carnitine?","a":"No. Carnitine is an amino-acid derivative involved in fat transport; carnosine is a dipeptide. The names get confused constantly."},{"q":"Is carnosine a peptide?","a":"Yes — the simplest kind, two amino acids: beta-alanine and histidine."}],"references":[{"cite":"Li N, et al. Effect of carnosine or beta-alanine supplementation therapy for prediabetes or type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.","where":"BMC Endocr Disord, 2025","url":"https://pubmed.ncbi.nlm.nih.gov/40999397/","note":"8 trials, 377 participants."},{"cite":"PubMed search: carnosine supplementation randomized trial cognition OR aging — no adequately powered trial of an ageing endpoint identified.","where":"PubMed, searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=carnosine+supplementation+randomized+cognition"}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade C on the 2025 meta-analysis."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"vilon","name":"Vilon","aliases":["Lys-Glu","lysyl-glutamic acid","thymic bioregulator dipeptide"],"url":"https://lyoresearch.com/compounds/vilon","class":{"id":"longevity-compounds","name":"Mitochondrial, antioxidant and longevity compounds","url":"https://lyoresearch.com/classes/longevity-compounds"},"summary":"Vilon is the dipeptide lysine–glutamate, one of the short synthetic peptides derived by Vladimir Khavinson's St Petersburg institute from thymic extracts and sold as an immune and anti-ageing 'bioregulator'. Its indexed evidence is mice — longer lifespan and fewer spontaneous tumours in the institute's own studies — and cultured cells. No human trial of any design exists. It is not approved anywhere this site covers.","overall_grade":"D","overall_grade_meaning":"no human evidence","human_trials":"0","regulatory_status":"Not approved","molecule":{"formula":"C11H21N3O5","molecular_weight":"275.30","cas":"45234-02-4","pubchem_cid":7010502,"note":"Recorded as lysylglutamic acid"},"pharmacokinetics":{"basis":"none","route":"Oral or injected as sold","half_life":"No human pharmacokinetic data","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Any outcome in humans","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"0","evidence":"A PubMed search returns 57 results, none a human trial. The 'chromatin reactivation' work used lymphocytes from elderly donors in culture.","references":[{"citation":"PubMed search: vilon Lys-Glu dipeptide — 57 results, no human trial.","where":"PubMed, searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=vilon+Lys-Glu+dipeptide"}]},{"outcome":"Lifespan and tumour incidence (mice)","grade":"D","grade_meaning":"no human evidence","effect_size":"moderate","adverse":false,"human_studies":"Animal only","evidence":"Female CBA mice given vilon from six months lived longer and developed fewer spontaneous tumours in the institute's studies; the same group reports opposite-direction effects in other models.","references":[{"citation":"Khavinson VK, et al. Effect of vilon on biological age and lifespan in mice.","where":"Bull Exp Biol Med, 2000","url":"https://pubmed.ncbi.nlm.nih.gov/11140587/"}]}],"regions":[{"region":"European Union","status":"Not authorised","note":"No marketing authorisation."},{"region":"United States","status":"Not approved","note":"Not FDA-approved."},{"region":"United Kingdom","status":"Not licensed","note":"Unlicensed."},{"region":"Australia","status":"Not on the ARTG","note":"Not registered."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved, so S0 (non-approved substances)."}],"faq":[{"q":"Does vilon boost immunity?","a":"In mice and cell culture, effects are reported by its developers. No human trial has tested it."},{"q":"Is vilon the same as thymalin?","a":"No. Thymalin is an undefined calf-thymus extract; vilon is a defined dipeptide the same group derived from it. Neither has a randomised human trial."}],"references":[{"cite":"PubMed search: vilon Lys-Glu dipeptide — 57 results, no human trial.","where":"PubMed, searched 2026-09-23","url":"https://pubmed.ncbi.nlm.nih.gov/?term=vilon+Lys-Glu+dipeptide"},{"cite":"Khavinson VK, et al. Effect of vilon on biological age and lifespan in mice.","where":"Bull Exp Biol Med, 2000","url":"https://pubmed.ncbi.nlm.nih.gov/11140587/","note":"Mice."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade D: no human study."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"},{"id":"cortexin","name":"Cortexin","aliases":["Korteksin","cortex polypeptides","porcine/bovine brain cortex peptide extract"],"url":"https://lyoresearch.com/compounds/cortexin","class":{"id":"nootropic-peptides","name":"Nootropic and sleep peptides","url":"https://lyoresearch.com/classes/nootropic-peptides"},"summary":"Cortexin is a mixture of low-molecular-weight peptides extracted from calf and pig brain cortex, registered in Russia and given by injection for stroke, brain injury and cognitive impairment. Its best evidence is a 272-patient double-blind, placebo-controlled trial in ischaemic stroke published in Russian in 2014, whose abstract reports 'high efficacy' without a primary endpoint or a figure. No trial has been published in an international journal. It is not approved anywhere this site covers.","overall_grade":"C","overall_grade_meaning":"weak human evidence","human_trials":"1 double-blind RCT (n=272, Russian); open trials","regulatory_status":"Not approved (Russia only)","molecule":{"formula":null,"molecular_weight":null,"cas":null,"pubchem_cid":null,"note":"An undefined mixture of brain-cortex peptides under 10 kDa — no molecular identity"},"pharmacokinetics":{"basis":"none","route":"Intramuscular as used clinically","half_life":"No pharmacokinetic data (an undefined peptide mixture)","licensed_regimen":null,"product":null,"source":null},"outcomes":[{"outcome":"Recovery after ischaemic stroke","grade":"C","grade_meaning":"weak human evidence","effect_size":"small","adverse":false,"human_studies":"1 double-blind RCT (n=272, 70 days)","evidence":"Two ten-day courses of 10 mg three times daily were compared with one course and with placebo. The abstract reports a benefit for two courses and recommends the drug; it gives no endpoint, effect size or statistics.","references":[{"citation":"Aliferova VM, et al. Clinical efficacy and pharmacoeconomic characteristics of the neuroprotection with low doses of cortexin in the treatment of acute ischemic stroke (in Russian).","where":"Zh Nevrol Psikhiatr Im S S Korsakova, 2014","url":"https://pubmed.ncbi.nlm.nih.gov/24874316/"}],"verbatim":{"text":"A multicenter prospective double-blind placebo-controlled trial has been carried out.","citation":"Aliferova VM, et al. Clinical efficacy and pharmacoeconomic characteristics of the neuroprotection with low doses of cortexin in the treatment of acute ischemic stroke (in Russian).","url":"https://pubmed.ncbi.nlm.nih.gov/24874316/"}},{"outcome":"Cognitive impairment","grade":"D","grade_meaning":"no human evidence","effect_size":"not measurable","adverse":false,"human_studies":"Open-label Russian reports","evidence":"Uncontrolled series in encephalopathy and after stroke; nothing that can be graded above D.","references":[{"citation":"Open clinical trial of cortexin in treatment of brain ischemia (in Russian).","where":"2014","url":"https://pubmed.ncbi.nlm.nih.gov/25403301/"}]}],"regions":[{"region":"European Union","status":"Not authorised","note":"No marketing authorisation; supply for human use is unlawful."},{"region":"United States","status":"Not approved","note":"Not FDA-approved."},{"region":"United Kingdom","status":"Not licensed","note":"Unlicensed medicine."},{"region":"Australia","status":"Not on the ARTG","note":"Not registered."},{"region":"Canada","status":"Not authorised","note":"No Drug Identification Number."},{"region":"Sport (WADA)","status":"Prohibited at all times","note":"Unapproved by any regulator WADA recognises, so S0 (non-approved substances)."}],"faq":[{"q":"Is cortexin the same as cerebrolysin?","a":"Same idea, different animal and maker: both are brain-peptide extracts from the Russian and Austrian traditions. Cerebrolysin has Cochrane reviews (negative or inconclusive); cortexin has one Russian trial."},{"q":"Does cortexin work for stroke?","a":"The one double-blind trial says yes in its abstract and gives no numbers. That is not enough to know."}],"references":[{"cite":"Aliferova VM, et al. Clinical efficacy and pharmacoeconomic characteristics of the neuroprotection with low doses of cortexin in the treatment of acute ischemic stroke (in Russian).","where":"Zh Nevrol Psikhiatr Im S S Korsakova, 2014","url":"https://pubmed.ncbi.nlm.nih.gov/24874316/","note":"272 patients; double-blind, placebo-controlled; abstract reports no figures."},{"cite":"Open clinical trial of cortexin in treatment of brain ischemia (in Russian).","where":"2014","url":"https://pubmed.ncbi.nlm.nih.gov/25403301/","note":"Uncontrolled."}],"last_reviewed":"2026-09-23","literature_searched_to":"2026-09-23","changelog":[{"date":"2026-09-23","note":"Initial publication. Grade C on one unreportable Russian RCT."}],"license":"CC BY 4.0 — cite as “LYO Research” with a link.","methodology":"https://lyoresearch.com/methodology"}]}