S2397 Real-World Benefits of GLP-1RA Therapy in MASLD: Reductions in Cardiovascular, Renal, Hepatic, and Mortality Outcomes

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) is linked to adverse cardiovascular, renal, and hepatic outcomes. GLP-1 receptor agonists (GLP-1RAs), such as semaglutide, dulaglutide, and tirzepatide, offer metabolic and anti-inflammatory effects that may mitigate disease progression. This study aimed to evaluate the association between GLP-1RA use and clinical outcomes in individuals with MASLD using a large population-based cohort. Methods: Adults with MASLD were identified from the TriNetX Global Network. Individuals with alcohol-related liver disease, type 1 diabetes, or liver transplant were excluded. GLP-1RA exposure was defined by prescription of semaglutide, dulaglutide, or tirzepatide. Patients were matched 1:1 using propensity scores based on demographics, comorbidities, and baseline labs. Primary outcomes included cardiovascular events, renal complications, liver-related outcomes, and mortality over a follow-up of up to 5 years. Results: After propensity matching, 211,640 patients were included in each group. GLP-1RA use was associated with significantly lower hazards for several outcomes: cardiac arrest (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.45–0.58), myocardial infarction (HR 0.87, 95% CI 0.82–0.92), ischemic stroke (HR 0.86, 95% CI 0.80–0.92), and heart failure (HR 0.84, 95% CI 0.80–0.88), all P < 0.001. Renal outcomes were also improved, with reduced hazards for dialysis (HR 0.64, 95% CI 0.57–0.72) and progression to advanced chronic kidney disease (HR 0.77, 95% CI 0.73–0.82), both P < 0.001. Hepatic complications were significantly reduced for ascites (HR 0.56, 95% CI 0.51–0.62) and spontaneous bacterial peritonitis (HR 0.43, 95% CI 0.30–0.62), but not for cirrhosis (HR 0.97, 95% CI 0.92–1.02), variceal bleeding (HR 0.90, 95% CI 0.75–1.09), or portal hypertension (HR 0.94, 95% CI 0.88–1.01). Elevated liver enzymes occurred less frequently (HR 0.58, 95% CI 0.54–0.63, P < 0.001), and all-cause mortality was substantially reduced (HR 0.39, 95% CI 0.37–0.42, P < 0.001). Conclusion: In this large, matched cohort of MASLD patients, GLP-1RA therapy was associated with reduced cardiovascular, renal, and hepatic complications and lower mortality. These findings support further prospective trials evaluating GLP-1RAs as potential disease-modifying agents in MASLD.