Incretin therapies significantly reduce liver enzymes and fat in MASLD, promoting steatohepatitis resolution

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver condition, often progressing to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. Current standard-of-care for MASLD is limited, focusing mainly on lifestyle changes, with no FDA-approved pharmacotherapy specifically for MASH. Incretin therapies, including GLP-1 receptor agonists (GLP-1RAs) and dual agonists, target metabolic dysfunction, which is central to MASLD pathogenesis, offering a promising therapeutic avenue. This meta-analysis evaluates their efficacy against standard therapies.

This systematic review and meta-analysis included 24 RCTs (n = 2158) involving adults with MASLD or biopsy-confirmed MASH. Researchers compared incretin therapies against placebo, oral hypoglycemic agents (OHAs), or insulin. Primary outcomes assessed were changes in liver enzymes (ALT, AST), liver fat, and fibrosis resolution. The systematic search covered databases from inception to August 2025, identifying eligible RCTs that enrolled adults with MASLD or biopsy-confirmed MASH.

Compared to placebo, incretin therapies significantly reduced ALT (SMD -0.46; 95% CI -0.67 to -0.25) and AST (SMD -0.41; 95% CI -0.66 to -0.17). Liver fat was also reduced (SMD -0.55; 95% CI -1.38 to 0.27). Incretin therapies improved non-invasive fibrosis markers. Steatohepatitis resolution was greater versus placebo, though not significantly different from insulin. Hepatic and steatohepatitis outcomes appeared more pronounced among patients with coexisting diabetes. The safety profile was acceptable across the studies.

When compared to insulin, incretin therapies demonstrated even greater reductions in 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).