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Compound monograph · evidence extract

Survodutide in metabolic dysfunction-associated steatohepatitis — evidence extract

The Institute's graded assessment of Survodutide for metabolic dysfunction-associated steatohepatitis, with the contributing trials and the domain-by-domain certainty reasoning.

Document identifier
CEI-MN-013/EV-MASH
Series
Evidence extract
Version
3.1
Published
19 Nov 2025
Last reviewed
19 Nov 2025
Next review
19 Nov 2027
Identifier
10.71829/cei.mono.13
Certainty
Low
Cycle
2025 Q4

§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
Survodutide, 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 Survodutide in metabolic dysfunction-associated steatohepatitis.

TrialPhaseDesignRandomisedDurationYear
LIVERAGE2Randomised, double-blind, placebo-controlled5248 weeks2016
SURVO-PH2-MASH2Randomised, double-blind, placebo-controlled29548 weeks2024

§1.3Certainty assessment

Certainty assessment by domainDowngrading decision recorded for each certainty domain.Certainty domainNo concernSeriousVery seriousEffect on ratingRisk of biasno downgradeInconsistencyno downgradeIndirectnessdowngrade two levelsImprecisionno downgradePublication biasno downgradeTotal downgrading: 2 levelsLow certainty
Figure 2. Domain-by-domain certainty assessment for Survodutide in metabolic dysfunction-associated steatohepatitis. The starting rating for a body of randomised evidence is high; each serious concern reduces it by one level and each very serious concern by two.

Table 2. Reasoning recorded against each certainty domain.

DomainRatingReasoning
Risk of biasNo concernNo serious concern identified in this domain.
InconsistencyNo concernNo serious concern identified in this domain.
IndirectnessVery seriousThe outcome is a surrogate whose relationship to the clinical outcome is unvalidated for this indication.
ImprecisionNo concernNo serious concern identified in this domain.
Publication biasNo concernNo 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.

  1. le Roux CW, Steen O, Lucas KJ, Startseva E, Unseld A, Hennige AM. Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial. The Lancet Diabetes & Endocrinology 2024;12(3):162–173. doi:10.1016/S2213-8587(23)00356-X · PMID 38330977
  2. Sanyal AJ, Bedossa P, Fraessdorf M, Neff GW, Lawitz E, Bugianesi E, Anstee QM, Hussain SA, Newsome PN, Ratziu V, Hosseini-Tabatabaei A, Schattenberg JM. A phase 2 randomized trial of survodutide in MASH and fibrosis. New England Journal of Medicine 2024;391(4):311–319. doi:10.1056/NEJMoa2401755 · PMID 38847460
  3. 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

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