TRIUMPH trial programme (revision 9)
Old revision·11:57, 30 Dec 2024·KarlFischerKit
| TRIUMPH trial programme | |
|---|---|
| Drug | Retatrutide |
| Indications studied | Obesity, type 2 diabetes, related conditions |
| Status | Ongoing; not approved |
| Topic infobox · conventions | |
The TRIUMPH trial programme is the phase 3 series evaluating retatrutide, an investigational triple agonist at the GIP, GLP-1 and glucagon receptors. The compound is not approved in any jurisdiction and the programme is ongoing.[1]
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.[1]
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.[2]
What phase 2 established
[edit]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.[1]
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.[3]
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.[2]
References
- ^ a b c 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.
- ^ a b 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.
- ^ International Council for Harmonisation, E9(R1): Estimands and Sensitivity Analysis in Clinical Trials (2019).