{"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"}