Retatrutide in metabolic dysfunction-associated steatohepatitis — evidence extract
The Institute's graded assessment of Retatrutide for metabolic dysfunction-associated steatohepatitis, with the contributing trials and the domain-by-domain certainty reasoning.
§1Evidence extract: Metabolic dysfunction-associated steatohepatitis
§1.1Question and anchor outcome
- Population
- Steatotic liver disease with histological evidence of hepatocyte ballooning and lobular inflammation occurring in the context of at least one cardiometabolic risk factor. Formerly termed non-alcoholic steatohepatitis.
- Intervention
- Retatrutide, subcutaneous once weekly
- Comparator
- As used in each contributing trial; reported per trial rather than pooled across comparator types
- Anchor outcome
- Resolution of steatohepatitis without worsening of fibrosis
Additional outcomes the Institute extracts for this indication: Improvement of fibrosis by ≥1 stage without worsening of steatohepatitis; Change in liver stiffness by vibration-controlled transient elastography; Change in ALT.
§1.2Contributing trials
Table 1. Trials contributing to the assessment of Retatrutide in metabolic dysfunction-associated steatohepatitis.
| Trial | Phase | Design | Randomised | Duration | Year |
|---|---|---|---|---|---|
| TRIUMPH-4 | 3 | Randomised, double-blind, placebo-controlled | — | 68 weeks or longer | — |
§1.3Certainty assessment
Table 2. Reasoning recorded against each certainty domain.
| Domain | Rating | Reasoning |
|---|---|---|
| Risk of bias | No concern | No serious concern identified in this domain. |
| Inconsistency | No concern | No serious concern identified in this domain. |
| Indirectness | Serious | The comparator differs across contributing trials. |
| Imprecision | Serious | The confidence interval spans values that would support different decisions. |
| Publication bias | No concern | No serious concern identified in this domain. |
| Overall rating: Low certainty. Confidence in the effect estimate is limited. The true effect may be substantially different from the estimate. | ||
§1.4What this extract does not establish
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
Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.