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 <0.001). A subgroup analysis excluding studies with patients with cirrhosis showed a significant benefit on fibrosis regression (OR: 2.02, 95% CI: 1.56–2.62, p =0.01). GLP-1RAs significantly improved nonalcoholic fatty liver disease activity scores and liver histologic features, including balloon degeneration, lobular inflammation, and steatosis, compared with placebo. The pooled serious adverse event rate for GLP-1RAs was comparable to placebo. Conclusions: In patients with noncirrhotic MASH, GLP-1RAs appear to be associated with both MASH resolution without fibrosis worsening and ≥1-stage fibrosis regression without MASH worsening.