Source of TRIUMPH trial programme

{{Infobox concept | name = TRIUMPH trial programme | subtitle = Phase 3 programme | Drug = [[Retatrutide|Retatrutide]] | Indications studied = Obesity, type 2 diabetes, related conditions | Status = Ongoing; not approved }} {{update|talk=Readouts pending}} The '''TRIUMPH trial programme''' is the phase 3 series evaluating [[Retatrutide|retatrutide]], an investigational triple agonist at the GIP, GLP-1 and [[Glucagon|glucagon]] receptors. The compound is not approved in any jurisdiction and the programme is ongoing.{{r|jastreboff2023}} The programme follows a phase 2 obesity trial that reported mean weight change of −24.2% at 48 weeks at the highest dose against −2.1% for placebo. Phase 2 effect sizes in this field have not always been reproduced at phase 3 scale, and this article will require revision as the programme reports.{{r|jastreboff2023}} Trials in the programme span obesity with and without type 2 diabetes and several related conditions, with durations longer than the 68- and 72-week designs of the earlier obesity programmes — a design choice consistent with a phase 2 weight curve that had not plateaued.{{r|coskun2022}} == What phase 2 established == The phase 2 trial randomised adults with obesity to placebo or one of several retatrutide doses, with escalation over 24 weeks and treatment to 48 weeks. Reported mean weight change ran from −8.7% at the lowest dose to −24.2% at the highest.{{r|jastreboff2023}} A phase 2 trial is powered for dose selection rather than for effect estimation, so the confidence intervals around the larger figures are wide and the point estimates are the least reliable part of the result. This is a general property of phase 2 rather than a criticism of this trial.{{r|ich_e9}} Two dose-related safety observations were reported: a heart-rate increase larger than that typical of GLP-1 monotherapy, and transient rises in fasting glucose at low doses in participants with diabetes. Both are attributable to the glucagon component and are the predicted consequences of the design.{{r|coskun2022}} == What phase 3 is designed to address == Phase 3 addresses the questions phase 2 cannot: effect size with adequate precision, safety at the event rates only large trials detect, durability over longer periods, and performance in the populations that will actually use the drug.{{r|ich_e9}} The heart-rate observation is the signal most likely to determine the risk–benefit assessment, since it is dose-related, mechanistically expected, and of a kind whose clinical consequences accumulate over years rather than weeks. Cardiovascular outcome evidence would require a dedicated trial of the kind run for [[Semaglutide|semaglutide]] as [[SELECT trial|SELECT]].{{r|lincoff2023}} Weight reduction is an intermediate endpoint and does not substitute for outcome data.{{r|ich_e9}} == Status and caution == Retatrutide is investigational. It is not approved anywhere, its phase 3 results are not fully published, and material sold under its name through research-chemical channels is an unapproved compound with no [[Reference standard|reference standard]] generally available for identity confirmation.{{r|jastreboff2023}} The {{tl-update}} tag on this article reflects a programme in progress. Figures quoted here are phase 2 figures and should not be treated as the expected phase 3 result. Nothing on this wiki is medical advice, and research-use compounds are not approved for human administration. See [[Research use only]].{{r|coskun2022}} == References == {{reflist}} <ref name="jastreboff2023">Jastreboff AM, Kaplan LM, Frías JP, et al. "Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial." ''New England Journal of Medicine'' 389(6):514–526 (2023). DOI:10.1056/NEJMoa2301972. PMID 37366315.</ref> <ref name="coskun2022">Coskun T, Urva S, Roell WC, et al. "LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss." ''Cell Metabolism'' 34(9):1234–1247 (2022). PMID 35985340.</ref> <ref name="ich_e9">International Council for Harmonisation, ''E9(R1): Estimands and Sensitivity Analysis in Clinical Trials'' (2019).</ref> <ref name="lincoff2023">Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. "Semaglutide and cardiovascular outcomes in obesity without diabetes." ''New England Journal of Medicine'' 389(24):2221–2232 (2023). PMID 37952131.</ref> == See also == * [[Retatrutide]] * [[SURMOUNT trial programme]] * [[SELECT trial]] * [[Glucagon]] * [[Triple agonist]] {{DEFAULTSORT:TRIUMPH trial programme}} [[Category:Clinical trial programmes]] [[Category:Obesity trials]] [[Category:Articles needing updates]]