Clinical evidence of semaglutide for metabolic dysfunction-associated steatotic liver disease (MASLD): An updated meta-analysis

In a pooled analysis of ten studies (1908 participants), semaglutide resolved steatohepatitis without worsening fibrosis and lowered liver stiffness, liver fat, and liver enzymes, but pooled fibrosis improvement was not statistically significant. Gastrointestinal adverse events were more common with semaglutide, while serious adverse events did not differ from control.

Meta-analysis — systematic review and meta-analysis. Population: people with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH). Sample size: 1908 participants (10 studies). Interventions: Semaglutide.

Semaglutide significantly improved MASH resolution without worsening fibrosis (OR 3.48; 95% CI 2.68-4.53; p < .00001). Pooled fibrosis improvement of ≥1 stage was not significant (OR 1.17; 95% CI 0.49-2.80; p = .72). Liver stiffness fell (MD -1.25 kPa; 95% CI -2.18 to -0.32; p = .009) and the odds of ≥30% relative liver fat reduction rose (OR 7.16; 95% CI 3.08-16.64; p < .00001). AST, ALT and cholesterol decreased. Gastrointestinal adverse events were more common (RR 1.83; 95% CI 1.20-2.79) but serious adverse events did not differ significantly (RR 1.07; 95% CI 0.82-1.39).

For researchers studying semaglutide, this meta-analysis consolidates evidence that the drug resolves steatohepatitis and improves imaging and biochemical markers while showing no significant overall effect on fibrosis stage. It suggests any anti-fibrotic benefit is limited to non-cirrhotic stages within the trial durations analysed and flags a higher risk of gastrointestinal adverse events. It does not establish doses, treatment duration, cirrhosis-specific efficacy, or long-term outcomes.

Key findings

• Semaglutide improved MASH resolution without worsening fibrosis (OR 3.48; 95% CI 2.68-4.53; p < .00001).
• Pooled fibrosis improvement of ≥1 stage was not statistically significant (OR 1.17; 95% CI 0.49-2.80; p = .72).
• Liver stiffness decreased by a mean difference of -1.25 kPa (95% CI -2.18 to -0.32; p = .009).
• The odds of ≥30% relative liver fat reduction increased (OR 7.16; 95% CI 3.08-16.64; p < .00001).
• AST, ALT and cholesterol were significantly reduced.
• Gastrointestinal adverse events were more frequent (RR 1.83; 95% CI 1.20-2.79) with no significant difference in serious adverse events (RR 1.07; 95% CI 0.82-1.39).

Limitations

• The authors note anti-fibrotic efficacy appears stage-dependent and time-dependent, with significant histological reversal primarily observed in non-cirrhotic stages within current trial durations.
• The pooled fibrosis-improvement result was not significant, so an anti-fibrotic effect is not established overall.
• As a meta-analysis, pooled estimates may be affected by heterogeneity among the ten included studies, and the abstract provides no trial durations or fibrosis-stage breakdown.

The record

• Journal: British journal of clinical pharmacology 92(8): 2584-2593
• Published: 2026-06-11
• PMID: 42273973 — DOI: 10.1002/bcp.70629
• MeSH terms: Liver, Humans, Fatty Liver, Liver Cirrhosis, Glucagon-Like Peptides, Non-alcoholic Fatty Liver Disease, Semaglutide
• Funding: Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
• Author countries: Taiwan

Peptide profiles: Semaglutide.

All indexed evidence: Semaglutide trials & papers.

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