Tirzepatide in metabolic dysfunction-associated steatohepatitis — evidence extract
The Institute's graded assessment of Tirzepatide 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
- Tirzepatide, 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 Tirzepatide in metabolic dysfunction-associated steatohepatitis.
| Trial | Phase | Design | Randomised | Duration | Year |
|---|---|---|---|---|---|
| SYNERGY-NASH | 2 | Randomised, double-blind, placebo-controlled | 190 | 52 weeks | 2024 |
§1.3Certainty assessment
Table 2. Reasoning recorded against each certainty domain.
| Domain | Rating | Reasoning |
|---|---|---|
| Risk of bias | Serious | Differential attrition exceeded the pre-specified threshold in one arm. |
| Inconsistency | Serious | Estimates vary in magnitude across contributing trials beyond what chance would produce. |
| Indirectness | No concern | No serious concern identified in this domain. |
| Imprecision | No concern | No serious concern identified in this domain. |
| 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, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A. Tirzepatide once weekly for the treatment of obesity. New England Journal of Medicine 2022;387(3):205–216. doi:10.1056/NEJMoa2206038 · PMID 35658024
- Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad NN, Bunck MC, Benabbad I, Zhang XM. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. The Lancet 2023;402(10402):613–626. doi:10.1016/S0140-6736(23)01200-X · PMID 37385275
- Wadden TA, Chao AM, Machineni S, Kushner R, Ard J, Srivastava G, Halpern B, Zhang S, Chen J, Bunck MC, Ahmad NN, Forrester T. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nature Medicine 2023;29(11):2909–2918. doi:10.1038/s41591-023-02597-w · PMID 37840095
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.