{"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"}