Safety and efficacy of semaglutide for non-alcoholic fatty liver disease: A meta-analysis of clinical outcomes

Non-alcoholic fatty liver disease (NAFLD) affects about 30.2% of the world and can progress from steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis, contributing substantially to mortality and disability-adjusted life years. Because no FDA-approved pharmacologic therapy exists, sustained weight loss and exercise remain the principal effective options. Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown potential benefits; therefore, we conducted a PRISMA- and PROSPERO-aligned systematic review and meta-analysis to evaluate its efficacy and safety in adults with NAFLD/NASH. PubMed, Scopus, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception to January 29, 2026 for randomized controlled trials comparing oral or injectable semaglutide with placebo or another intervention; screening was performed in Rayyan. Efficacy outcomes included changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and complete NASH resolution when reported; safety outcomes included adverse events, particularly diarrhea, nausea, vomiting, and nasopharyngitis. Data were synthesized in R (v4.4.2) with p<0.05. Effect estimates were pooled as standardized mean differences for transaminases, using random-effects models to account for clinical diversity. NASH-resolution data were insufficient for meaningful pooled analysis. Six trials comprising 1,980 participants were included. Semaglutide significantly reduced ALT (SMD −0.74, 95% CI −1.11 to −0.36; p=0.0001) and AST (SMD −0.63, 95% CI −1.01 to −0.24; p=0.0014). However, semaglutide increased gastrointestinal adverse events, including diarrhea, nausea, and vomiting. Overall, semaglutide improves liver transaminases in adults with NAFLD/NASH but at the cost of higher rates of common adverse effects; larger and longer trials with standardized histologic and clinical endpoints are needed to define net benefit.