Glucagon-like peptide-1 receptor agonists improve metabolic dysfunction-associated steatotic liver disease outcomes

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is associated with significant cardiovascular morbidity and mortality. This study aims to investigate the association of glucagon-like peptide-1 (GLP-1) agonists with major cardiovascular events, clinically significant portal hypertension events, and all-cause mortality in patients with MASLD. A large, population-based retrospective cohort study was conducted using the TriNetX platform, which provided real-time access to electronic health records of 634,265 adult patients with MASLD/MASH. Propensity score matching (PSM) was employed to create two cohorts: A GLP-1 agonists group and a control group without GLP-1 agonists usage. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models along with Kaplan-Meier survival analyses to estimate outcomes at the end of 1, 3, 5, and 7 years. After PSM, 6,243 patients were included in each group. The GLP-1 agonist group had significantly lower risk of heart failure (at 7 years, HR, 0.721; 95% Cl, 0.593-0.876), composite cardiovascular events (at years 7, HR, 0.594; 95% Cl, 0.475-0.745), clinically significant portal hypertension events (at 7 years, HR, 0.463; 95% Cl, 0.348-0.611), and all-cause mortality (at 7 years, HR, 0.303; 95% Cl, 0.239-0.385). These results were consistent at 1-, 3-, 5-, and 7-years post index event. GLP-1 agonists usage in patients with MASLD is associated with reduced risk of major cardiovascular events, clinically significant portal hypertension, and all-cause mortality. These findings highlight the potential of GLP-1 agonists in MASLD/MASH management, warranting further prospective studies.