{"id":"tirzepatide","name":"Tirzepatide","aliases":["Mounjaro","Zepbound","dual GIP/GLP-1 agonist"],"url":"https://lyoresearch.com/compounds/tirzepatide","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 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)","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/?term=Jastreboff+SURMOUNT-1+tirzepatide+2022"},{"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/"}]},{"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/?term=Frias+SURPASS-2+tirzepatide+semaglutide+2021"}]},{"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/?term=Malhotra+SURMOUNT-OSA+tirzepatide+2024"}]},{"outcome":"Cardiovascular events","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":false,"human_studies":"1 outcomes RCT (2025)","evidence":"SURPASS-CVOT reported tirzepatide non-inferior to dulaglutide on major adverse cardiovascular events in type 2 diabetes; superiority over an active GLP-1 comparator was not shown.","references":[{"citation":"Eli Lilly. SURPASS-CVOT topline: tirzepatide vs dulaglutide on cardiovascular outcomes in type 2 diabetes.","where":"Press release, 2025; full publication pending at time of review","url":"https://pubmed.ncbi.nlm.nih.gov/?term=SURPASS-CVOT+tirzepatide+dulaglutide"}]},{"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/?term=Jastreboff+SURMOUNT-1+tirzepatide+2022"},{"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/"}]}],"regions":[{"region":"European Union","status":"Approved, prescription-only","note":"Mounjaro is authorised by the EMA for type 2 diabetes and weight management."},{"region":"United States","status":"Approved, prescription-only","note":"Mounjaro (diabetes), Zepbound (obesity, sleep apnoea). Compounded copies were permitted during shortage and are now restricted."},{"region":"United Kingdom","status":"Approved, prescription-only","note":"NHS rollout for obesity began in 2025 under eligibility criteria."},{"region":"Sweden","status":"Approved, prescription-only","note":"Subsidy differs between diabetes and weight-management use."}],"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/?term=Jastreboff+SURMOUNT-1+tirzepatide+2022","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/?term=Frias+SURPASS-2+tirzepatide+semaglutide+2021","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/?term=Malhotra+SURMOUNT-OSA+tirzepatide+2024","note":"Two trials, 469 adults; basis of the sleep-apnoea approval."},{"cite":"Eli Lilly. SURPASS-CVOT topline: tirzepatide vs dulaglutide on cardiovascular outcomes in type 2 diabetes.","where":"Press release, 2025; full publication pending at time of review","url":"https://pubmed.ncbi.nlm.nih.gov/?term=SURPASS-CVOT+tirzepatide+dulaglutide","note":"Non-inferiority met; graded B until peer-reviewed."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"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"}