Incretin receptor agonists for metabolic dysfunction-associated steatohepatitis
In adults with metabolic dysfunction-associated steatohepatitis, do incretin receptor agonists improve histological outcomes, and does histological improvement predict clinical benefit?
§1Abstract
§1.1Review question
In adults with metabolic dysfunction-associated steatohepatitis, do incretin receptor agonists improve histological outcomes, and does histological improvement predict clinical benefit?
§1.2PICO frame
Table 1. The registered PICO frame. Any change made after protocol registration is recorded in the amendment log at §5 and is identified there as post hoc.
| Element | As registered |
|---|---|
| Population | Adults with biopsy-confirmed metabolic dysfunction-associated steatohepatitis with fibrosis stage 2 or 3. |
| Intervention | An incretin receptor agonist at an evaluated dose. |
| Comparator | Placebo. |
| Outcomes | Resolution of steatohepatitis without worsening of fibrosis; improvement in fibrosis without worsening of steatohepatitis; progression to cirrhosis; liver-related clinical events. |
§1.3Method in brief
A review of the effects of an intervention on pre-specified outcomes, with a quantitative synthesis where the contributing studies are sufficiently similar. The protocol was registered with the Institute's secretariat before the search was executed. The search was run on 13 November 2025 across 8 sources and is reproduced in full at §2. Screening, extraction and certainty assessment were performed independently by two members of the secretariat with disagreement resolved by a third.[1]
§1.4Conclusion
Moderate certainty evidence indicates that incretin receptor agonists produce resolution of steatohepatitis without worsening of fibrosis substantially more often than placebo at 48 to 72 weeks. Whether that histological change translates into a reduction in cirrhosis, hepatic decompensation or liver-related death is not established by any completed trial, and the Institute grades the clinical question as very low certainty for absence of evidence rather than as moderate by inheritance from the histological result.
The conclusion rests on 3 contributing studies, listed with their extracted data at §3 and summarised outcome by outcome at §4.
§1.5Limitations
§1.6Consultation
This review was released for public comment before ratification. Draft synthesis: incretin receptor agonists for metabolic dysfunction-associated steatohepatitis received 12 submissions. Amendments arising are recorded in the amendment log and are traceable to a numbered submission.
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.
- Sanyal AJ, Newsome PN, Kliers I, Østergaard LH, Long MT, Kjær MS, Cali AMG, Bugianesi E, Rinella ME, Roden M, Ratziu V. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. New England Journal of Medicine 2025;392(21):2089–2099. doi:10.1056/NEJMoa2413258
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.