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

This updated systematic review and meta-analysis evaluated the efficacy and safety of semaglutide — a GLP-1 receptor agonist — in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH). Following PRISMA guidelines and registered on PROSPERO, the authors searched multiple databases through January 2026, ultimately pooling data from 10 studies comprising 1,908 participants. The primary outcomes were histological MASH resolution without worsening of fibrosis and improvement in fibrosis stage; secondary outcomes included liver stiffness and biochemical markers. The meta-analysis found that semaglutide was significantly associated with MASH resolution without fibrosis worsening (OR 3.48; 95% CI: 2.68–4.53). However, the anti-fibrotic effect appeared to be both stage-dependent and time-dependent, with meaningful histological fibrosis reversal observed primarily in non-cirrhotic patients within the durations of the included trials. Improvements in liver stiffness and biochemical markers were also reported. Limitations include the relatively short durations of the constituent trials and heterogeneity across included studies, which may limit generalizability to advanced or cirrhotic disease stages.

Why this grade: Although pooling human trial data (n=1,908) via meta-analysis strengthens inference, the grade is moderate rather than strong due to the limited number of included studies (10), heterogeneity across trials, short trial durations for a fibrotic endpoint, and the stage-dependent limitations in anti-fibrotic conclusions.