Impact of incretin therapies on biochemical and imaging outcomes in metabolic dysfunction–associated steatotic liver disease

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition. Incretin therapies, including glucagon-like peptide-1 receptor agonists (GLP-1RAs) and emerging dual agonists, have shown promise in improving steatohepatitis. Objective: This study aims to evaluate the efficacy and safety of incretin therapies compared with standard therapies in patients with MASLD. Methods: Systematic search of Randomized Controlled Trials (RCTs) from database inception to August 2025 was done. Eligible RCTs enrolled adults with MASLD or biopsy-confirmed metabolic dysfunction-associated steatohepatitis (MASH), comparing incretin therapies with placebo, oral hypoglycemic agents (OHAs), or insulin. Outcomes were changes in liver enzymes, liver fat, and fibrosis resolution. Results: Twenty-four RCTs (n = 2158) were included. Compared with placebo, incretin therapies reduced ALT (SMD -0.46; 95 % CI -0.67 to -0.25), AST (SMD -0.41; 95 % CI -0.66 to -0.17), and liver fat (SMD -0.55; 95 % CI -1.38 to 0.27). When compared to insulin, ALT (SMD -1.02; 95 % CI -1.98 to -0.05), AST (SMD -0.62; 95 % CI -1.21 to -0.04), and liver fat (SMD -0.62; 95 % CI -0.92 to -0.32) were significantly reduced. Incretin therapies improved non-invasive fibrosis markers. Steatohepatitis resolution was greater vs placebo but not insulin. Hepatic and steatohepatitis outcomes appeared greater among patients with diabetes. Conclusion: Incretin therapies improve liver enzymes, reduce liver fat, and promote steatohepatitis resolution in MASLD with an acceptable safety profile. Benefits may be greater in patients with coexisting diabetes. Effects on histologic fibrosis remain inconclusive, underscoring the need for larger and longer trials.