The impact of semaglutide on liver outcomes in patients with or at risk of MASH: a dose and duration response meta-analysis of randomized trials.

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease associated with significant morbidity and mortality, yet management options remain limited. Although glucagon-like peptide-1 receptor agonists such as semaglutide have shown benefits in metabolic health, their efficacy and safety in patients with MASH require further elucidation. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) evaluating semaglutide in patients with MASH from inception through August 23, 2025. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 22 RCTs involving 32,013 patients were included. Semaglutide significantly improved MASH Resolution (RR = 1.98, 95%CI: 1.57 to 2.50) but did not yield significant improvement in Fibrosis Regression (RR = 1.18, 95%CI: 0.74 to 1.88). Semaglutide also reduced Liver Steatosis (WMD = -11.30%, 95%CI: -18.70 to -3.91) and the Enhanced Liver Fibrosis (ELF) score (WMD = -0.49, 95%CI: -0.70 to -0.29). Significant reductions were observed in liver enzymes, including alanine aminotransferase (ALT; WMD = -5.55 U/L, 95%CI: -9.21 to -1.89) and aspartate aminotransferase (AST; WMD = -3.85 U/L, 95%CI: -7.67 to -0.03). Additionally, semaglutide improved weight management, glycemic and lipid parameters, and reduced all-cause mortality (RR = 0.82, 95%CI: 0.74 to 0.91) and cardiovascular risk (RR = 0.83, 95%CI: 0.75 to 0.92). Subgroup analyses revealed the greatest benefits in patients receiving higher doses (≥ 2.0 mg weekly) and longer intervention durations (≥12 months). CONCLUSION: Semaglutide represents a promising pharmacotherapeutic option for MASH, demonstrating significant improvements in histologic resolution, liver injury biomarkers, and metabolic parameters, particularly at higher doses and longer intervention durations, though its effect on fibrosis regression remains limited.