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

BACKGROUND

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are major health burdens. Previous reviews of semaglutide found inconsistent fibrosis improvement. This study aims to provide updated evidence on the efficacy and safety of semaglutide in MASH through a systematic review and meta-analysis.

METHODS

Following PRISMA guidelines (PROSPERO: CRD420261288562), we searched databases through 8 January 2026. Ten studies (n = 1908) were analysed. Primary outcomes were histological MASH resolution and fibrosis improvement; secondary outcomes included liver stiffness and biochemical markers.

RESULTS

Semaglutide significantly improved MASH resolution without worsening fibrosis (OR 3.48; 95% CI: 2.68-4.53; p < .00001). However, pooled fibrosis improvement (≥1 stage) was not statistically significant (OR 1.17; 95% CI: 0.49-2.80; p = .72). Radiologically, semaglutide reduced liver stiffness (MD -1.25 kPa; 95% CI: -2.18 to -0.32; p = .009) and increased relative liver fat reduction of ≥30% (OR 7.16; 95% CI: 3.08-16.64; p < .00001). Significant reductions in AST, ALT and cholesterol were also observed. Regarding safety, semaglutide was associated with a higher risk of gastrointestinal-related adverse events (RR = 1.83; 95% CI: 1.20-2.79) compared with the control group, but no significant difference was observed in the risk of serious adverse events (RR = 1.07; 95% CI: 0.82-1.39).

CONCLUSION

Semaglutide effectively resolves steatohepatitis and improves biochemical and imaging markers. However, its anti-fibrotic efficacy appears stage-dependent and time-dependent, with significant histological reversal primarily observed in non-cirrhotic stages within current trial durations.