{"id":"retatrutide","name":"Retatrutide","aliases":["LY3437943","triple agonist","GIP/GLP-1/glucagon agonist"],"url":"https://lyoresearch.com/compounds/retatrutide","summary":"Retatrutide is an investigational once-weekly peptide that activates three receptors at once: GIP, GLP-1 and glucagon. Phase 3 topline results announced in December 2025 and May 2026 report average weight loss of about 26–29% at 68–80 weeks — the largest yet for a single drug — with high rates of nausea and more people stopping for side effects than on placebo. The full data are not yet peer-reviewed. It is not approved anywhere, and no legitimate supply exists outside clinical trials.","overall_grade":"B","overall_grade_meaning":"probable, not settled","human_trials":"Phase 3 topline","regulatory_status":"Investigational","outcomes":[{"outcome":"Body weight","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":false,"human_studies":"1 phase 2 RCT published; 2 phase 3 RCTs topline","evidence":"Phase 2: −24.2% at 48 weeks on 12 mg. Phase 3 TRIUMPH-4: −28.7% at 68 weeks vs −2.1% placebo. TRIUMPH-1 (2,339 adults): −28.3% at 80 weeks on 12 mg, −30.3% at 104 weeks in the BMI ≥35 extension. Press releases; peer review pending.","references":[{"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/?term=Jastreboff+retatrutide+phase+2+obesity+2023"},{"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"}]},{"outcome":"Knee osteoarthritis pain","grade":"B","grade_meaning":"probable, not settled","effect_size":"moderate","adverse":false,"human_studies":"1 phase 3 RCT topline","evidence":"TRIUMPH-4 enrolled adults with obesity and knee osteoarthritis: WOMAC pain fell by up to 4.5 points (75.8%) vs 2.4 (40.3%) on placebo. Weight loss likely explains much of it; not yet peer-reviewed.","references":[{"citation":"Eli Lilly.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"}]},{"outcome":"GI side effects","grade":"B","grade_meaning":"probable, not settled","effect_size":"large","adverse":true,"human_studies":"Phase 2 + phase 3 topline","evidence":"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.","references":[{"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/?term=Jastreboff+retatrutide+phase+2+obesity+2023"},{"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"}]},{"outcome":"Dysesthesia (skin sensation changes)","grade":"B","grade_meaning":"probable, not settled","effect_size":"small","adverse":true,"human_studies":"Phase 3 topline","evidence":"Reported in 9–21% of treated participants vs 0.7% on placebo in TRIUMPH-4 — an effect not prominent with older GLP-1 drugs.","references":[{"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"}]}],"regions":[{"region":"European Union","status":"Not authorised — investigational","note":"No marketing application decided. Any product sold as retatrutide in the EU is an unlicensed medicine of unknown provenance."},{"region":"United States","status":"Not approved — in phase 3","note":"Available only inside clinical trials. Lilly has said it expects to file for approval after the TRIUMPH programme completes."},{"region":"United Kingdom","status":"Not authorised","note":"MHRA has warned about unlicensed weight-loss injectables sold online."},{"region":"Sweden","status":"Not authorised","note":"Not on the Läkemedelsverket register; cannot be prescribed."}],"faq":[{"q":"How much weight do people lose on retatrutide?","a":"In the phase 3 TRIUMPH-1 topline, adults on the 12 mg dose lost 28.3% of body weight on average over 80 weeks, and 30.3% at 104 weeks in a heavier subgroup. In phase 2 the figure was 24.2% at 48 weeks. These are averages from press releases; the peer-reviewed papers will give the spread."},{"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 grade B and not A?","a":"Because the phase 3 results exist only as company press releases. LYO's A grade requires peer-reviewed publication of multiple trials. The grade will be reviewed when the TRIUMPH papers appear."}],"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/?term=Jastreboff+retatrutide+phase+2+obesity+2023","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."}],"last_reviewed":"2026-09-02","literature_searched_to":"2026-09-02","changelog":[{"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"}