Efficacy of GLP-1 Receptor Agonists for Fibrosis Regression in Patients with MASH and F2-F3 Fibrosis: A Systematic Review and Meta-Analysis

Background Metabolic dysfunction-associated steatohepatitis (MASH) with significant to advanced fibrosis (F2–F3) confers a substantial risk of progression to cirrhosis and liver-related complications. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as promising therapies for metabolic disease, yet their effect on histologic fibrosis regression in this high-risk population requires clarification. Methods Following the PRISMA 2020 guidelines, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) by searching PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov through December 2025. Eligible studies were parallel-group RCTs evaluating GLP-1 RAs in adults with biopsy-confirmed MASH and F2–F3 fibrosis. The primary outcome was fibrosis regression of at least one stage without worsening of MASH. The secondary outcome was MASH resolution without worsening of fibrosis. Data were pooled using a random-effects model and reported as risk ratios (RRs) with 95% confidence intervals (CIs). Results Six RCTs comprising 1,955 patients met inclusion criteria. Treatment with GLP-1 RAs significantly increased the likelihood of fibrosis regression compared with placebo (RR 1.62; 95% CI, 1.36–1.92; P < 0.001; I 2 = 0.0%), demonstrating consistent effects across trials. GLP-1 RAs also significantly improved MASH resolution (RR 3.55; 95% CI, 2.14–5.88; P < 0.001; I 2 = 73.1%), although heterogeneity was observed for this endpoint. Conclusion In patients with MASH and F2–F3 fibrosis, GLP-1 receptor agonists produce statistically significant and clinically meaningful improvements in liver fibrosis and steatohepatitis. These findings support their role as a therapeutic strategy to modify disease progression in this high-risk metabolic population.