Efficacy and safety of GLP-1 receptor agonists in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH): A systematic review and meta-analysis.

Abstract

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are increasingly prevalent liver diseases closely linked to obesity, type 2 diabetes mellitus, and cardiometabolic risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may improve hepatic and metabolic outcomes through weight reduction, improved glycemic control, and reductions in hepatic steatosis. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of GLP-1 RAs in adults with MASLD or MASH.

Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched for English-language studies published between January 2019 and December 2025. Eligible studies included adults with MASLD or MASH treated with GLP-1 RAs and reporting hepatic, metabolic, or safety outcomes. Pooled estimates were calculated using random-effects models.

Results: Nine studies involving 795 participants were included. GLP-1 RA therapy was associated with significant reductions in liver fat content (mean difference [MD]: -3.17; 95% CI: -4.06 to -2.29), body weight (MD: -4.68; 95% CI: -6.88 to -2.47), alanine aminotransferase (MD: -15.17; 95% CI: -21.29 to -9.05), aspartate aminotransferase (MD: -9.89; 95% CI: -13.65 to -6.13), and HbA1c (MD: -0.78; 95% CI: -1.07 to -0.49). Adverse events were more frequent with GLP-1 RAs, particularly nausea and vomiting, while serious adverse events did not differ significantly between groups.

Conclusion: GLP-1 RAs are associated with meaningful improvements in hepatic steatosis, liver enzymes, body weight, and glycemic control in patients with MASLD or MASH. These findings support their potential role, particularly in patients with coexisting obesity or type 2 diabetes. However, further long-term, adequately powered trials are needed to clarify their effects on fibrosis regression, histological outcomes, and liver-related clinical events.