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Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Evidence synthesis · §4

Incretin receptor agonists for metabolic dysfunction-associated steatohepatitis — summary of findings

Outcome-by-outcome summary with effect, certainty and the reason for each downgrade.

Document identifier
CEI-ES-010/4
Series
Evidence synthesis
Version
3.2
Published
12 Jan 2026
Last reviewed
12 Jan 2026
Next review
12 Jul 2027
Identifier
10.71829/cei.syn.10
Certainty
Moderate
Cycle
2026 Q1
Review type
Intervention review
Search executed
13 Nov 2025

§4Summary of findings

§4.1Summary of findings

Table 7. Summary of findings for Incretin receptor agonists for metabolic dysfunction-associated steatohepatitis.

OutcomeParticipants (studies)Effect as reportedCertaintyReason for downgrade
Resolution of steatohepatitis without worsening of fibrosisThe outcome the Institute designates as anchor for this indication.1,682 (3)Moderate certainty evidence indicates that incretin receptor agonists produce resolution of steatohepatitis without worsening of fibrosis…Moderatepublication bias
Discontinuation for adverse eventsReported as a summary-of-findings row rather than in a tolerability annex, following a public submission.1,251 (1)Reported per contributing trial; see the included-studies tableModeraterisk of bias
Serious adverse eventsEvent counts are low; the estimate is imprecise by construction.1,588 (1)Reported per contributing trial; see the included-studies tableLowrisk of bias, imprecision
Any adverse eventAscertained by spontaneous report in the contributing trials.1,286 (1)Reported per contributing trial; see the included-studies tableLowinconsistency, indirectness
Improvement of fibrosis by ≥1 stage without worsening of steatohepatitisA secondary outcome for this indication. Its hierarchical position within each contributing trial is recorded on that trial's abstract where the Institute holds it.1,026 (2)Reported as a secondary outcome in a subset of contributing trialsLowrisk of bias, imprecision
Change in liver stiffness by vibration-controlled transient elastographyA secondary outcome for this indication. Its hierarchical position within each contributing trial is recorded on that trial's abstract where the Institute holds it.1,126 (2)Reported as a secondary outcome in a subset of contributing trialsLowinconsistency, publication bias
Certainty ratings describe confidence in the effect estimate for the stated outcome. They are not recommendations and do not transfer between outcomes.

§4.2Forest plot

Contributing estimatesPoint estimates with confidence intervals for each contributing study, plotted against the line of no effect.0.751Ratio measure, log scale (1 = no effect)Contributing studyEstimate (95 % CI)ESSENCE2025 · n=1,1970.81 (0.67 to 0.96)SURVO-PH2-MASH2024 · n=2951.03 (0.75 to 1.31)SYNERGY-NASH2024 · n=1900.86 (0.77 to 0.96)Pooled estimate0.92 (0.81 to 1.04)
Study estimatePooled estimate
Figure 1. Illustrative. Contributing estimates plotted against the line of no effect. The point estimates and intervals are the Institute's standardised representation of the contributing evidence on a common ratio scale, generated deterministically from the record identifiers; they are not the published estimates, which appear in their own units in the included-studies table and on each trial abstract. The figure is published to convey the dispersion of the evidence base, not to supply a number.

§4.3Certainty assessment for the anchor outcome

Certainty assessment by domainDowngrading decision recorded for each certainty domain.Certainty domainNo concernSeriousVery seriousEffect on ratingRisk of biasno downgradeInconsistencyno downgradeIndirectnessno downgradeImprecisionno downgradePublication biasdowngrade one levelTotal downgrading: 1 levelModerate certainty
Figure 2. Domain-by-domain certainty assessment for the anchor outcome of this review.

Table 8. Reasoning recorded against each certainty domain for the anchor outcome.

DomainRatingReasoning
Risk of biasNo concernNo serious concern identified in this domain.
InconsistencyNo concernNo serious concern identified in this domain.
IndirectnessNo concernNo serious concern identified in this domain.
ImprecisionNo concernNo serious concern identified in this domain.
Publication biasSeriousToo few contributing studies for a formal assessment; the risk cannot be excluded.
Overall: Moderate certainty. The true effect is likely to be close to the estimate, but there is a possibility that it is substantially different. Further research is likely to have an important impact on confidence in the estimate.

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.

  1. 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.

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