Effect of glucagon-like peptide-1 receptor agonists on histologic MASH: A meta-analysis of randomized controlled trials

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is the most common chronic liver disease worldwide, with a particularly high incidence among individuals with type 2 diabetes and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as effective weight loss agents, with growing evidence suggesting potential benefits in MASH. This study aimed to evaluate the efficacy and safety of GLP-1RAs in improving the histologic features of MASH. METHODS: This study is a meta-analysis of randomized controlled trials evaluating the effect of FDA-approved GLP-1RAs in patients with biopsy-confirmed MASH, up to May 2025. The primary outcomes were resolution of MASH without worsening of fibrosis and a ≥1 improvement in fibrosis stage without worsening of MASH at 12-18 months. Secondary outcomes included ≥1-point improvements in the nonalcoholic fatty liver disease activity score, changes in liver histologic features, and the incidence of serious adverse events. RESULTS: A total of 6 randomized controlled trials with 1555 patients (1082 GLP-1RA and 473 placebo) with MASH were included. At 18 months, a significantly greater proportion of patients in the GLP-1RA group achieved MASH resolution without worsening fibrosis compared with the placebo group (OR: 4.16, 95% CI: 2.33-7.42, p