Retatrutide — clinical evidence
Assessed outcomes with certainty ratings, contributing trials and the reasoning for each rating.
§3Clinical evidence
§3.1Obesity and overweight in adults
Anchor outcome. Percentage change in body weight from baseline.
Effect as recorded. −24.2 % body weight at 48 weeks with 12 mg in the phase 2 trial versus −2.1 % with placebo; least-squares mean difference −22.1 percentage points (95 % CI −25.0 to −19.2).[1,2]
Certainty. Moderate certainty The largest weight effect reported for any single agent, but from a phase 2 trial of 338 participants. Downgraded from high for indirectness of dose and imprecision at the extremes; phase 3 confirmation was pending at this assessment cycle.
Contributing trials. TRIUMPH-1 · TRIUMPH-3 · RETA-PH2-OBESITY. Full structured abstracts are published for each.
Full evidence extract for obesity and overweight in adults · Indication assessment
§3.2Type 2 diabetes mellitus
Anchor outcome. Change in HbA1c (%, mmol/mol).
Effect as recorded. −2.02 % HbA1c at 36 weeks with 12 mg versus −0.01 % with placebo; weight −16.9 %; estimated difference −2.02 % (95 % CI −2.45 to −1.59).[2,3]
Certainty. Moderate certainty Phase 2, active- and placebo-controlled with dulaglutide 1.5 mg as reference.
Contributing trials. TRIUMPH-2 · RETA-PH2-T2D. Full structured abstracts are published for each.
Full evidence extract for type 2 diabetes mellitus · Indication assessment
§3.3Metabolic dysfunction-associated steatohepatitis
Anchor outcome. Resolution of steatohepatitis without worsening of fibrosis.
Effect as recorded. Liver-fat reduction exceeding 80 % relative at higher doses in a phase 2 imaging substudy; substudy; MRI-PDFF endpoint.[3,4]
Certainty. Low certainty Imaging surrogate only; no histological endpoint reported.
Contributing trials. TRIUMPH-4. Full structured abstracts are published for each.
Full evidence extract for metabolic dysfunction-associated steatohepatitis · Indication assessment
§3.4Obstructive sleep apnoea with obesity
Anchor outcome. Change in apnoea–hypopnoea index (events/hour).
Effect as recorded. Not yet reported; —.[4,5]
Certainty. Not rated certainty Registered but unreported at this assessment cycle.
Contributing trials. TRIUMPH-OSA. Full structured abstracts are published for each.
Full evidence extract for obstructive sleep apnoea with obesity · Indication assessment
References cited on this page
References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.
- Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. New England Journal of Medicine 2023;389(6):514–526. doi:10.1056/NEJMoa2301972 · PMID 37366315
- Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, Coskun T. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo- and active-controlled, parallel-group, phase 2 trial. The Lancet 2023;402(10401):529–544. doi:10.1016/S0140-6736(23)01053-X · PMID 37385280
- Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D’Alessio DA, Haupt A. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: from discovery to clinical proof of concept. Molecular Metabolism 2018;18:3–14. doi:10.1016/j.molmet.2018.09.009 · PMID 30473097
- Müller TD, Finan B, Bloom SR, D’Alessio D, Drucker DJ, Flatt PR, Fritsche A, Gribble F, Grill HJ, Habener JF, Holst JJ, Langhans W, Meier JJ, Nauck MA, Perez-Tilve D, Pocai A, Reimann F, Sandoval DA, Schwartz TW, Seeley RJ. Glucagon-like peptide 1 (GLP-1). Molecular Metabolism 2019;30:72–130. doi:10.1016/j.molmet.2019.09.010 · PMID 31767182
- Bhattacharyya S, Wang J, Kaplan RM. Quality of peptide products obtained from unregulated online suppliers: an analytical survey. Journal of Pharmaceutical Sciences 2024;113(4):1102–1110. doi:10.1016/j.xphs.2023.11.021 Cited by the Institute as an indicative analytical survey; sample frame was not random.
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