S2523 Long Term Cardiovascular Outcomes in Patients With MASLD Who Also Have Obesity and are Overweight Who Underwent Semaglutide Therapy

Introduction: GLP-1 receptor agonists, initially for type 2 diabetes, are now recognized for benefits in metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular health. MASLD significantly increases cardiovascular disease (CVD) risk, including ACS, stroke/TIA, and atrial fibrillation—often the leading cause of death in MASLD patients. This study examines semaglutide’s impact on cardiovascular outcomes in overweight and obese MASLD patients versus those untreated. Methods: We conducted a retrospective cohort study using TriNetX and identified MASLD patients with overweight and obesity who received GLP-1RA (Group A) versus those who did not (Group B). The primary outcomes included the incidence of TIA, CVA, STEMI/NSTEMI, Heart failure, atrial fibrillation, ventricular tachycardia, and all-cause mortality over 20 years following the index event. Patients with outcomes before the study window were excluded. Propensity score matching was utilized to adjust for potential confounders, including age, viral hepatitis, alcoholic liver disease, and autoimmune hepatitis. Multivariate logistic regression was performed to determine associations between GLP-1RA use and cardiovascular disease outcomes over a 20-year follow-up period, reporting risk ratios (RR) with 95% confidence intervals (CI). Results: Following propensity score matching, each cohort included 67,679 patients. The mean age in Group A was 55.7 ± 13.8 years (60.7% woman, 71.1% White),while Group B had a mean age of 56.9 ± 16.6 years (55.4% woman, 69.0% White). At 20 years, GLP-1RA use was associated with lower incidence of: TIA (438 vs 573 cases, RR: 0.760 [95% CI: 0.671-0.860]), CVA (1554 vs 1842 cases, RR: 0.823 [95% CI: 0.770–0.880]), STEMI/NSTEMI (792 vs 1017 cases, RR: 0.771 [95% CI: 0.703–0.846]), Heart failure (1,541 vs 1911 cases, RR: 0.797 [95% CI: 0.746–0.852]), atrial fibrillation (1,070 vs 1,281 cases, RR: 0.818 [95% CI: 0.755–0.886]), ventricular tachycardia (405 vs 524 cases, RR: 0.770 [95% CI: 0.677–0.876]), and all-cause mortality (991 vs 2485 cases, RR: 0.399 [95% CI: 0.371–0.429]). The absolute risk reduction for mortality was 2.2%, translating to a number needed to treat (NNT) of 45 to prevent 1 death. Conclusion: GLP-1RA use in overweight and obese MASLD patients reduced cardiovascular complications and mortality over 20 years. These findings underscore metabolic interventions’ role in hepatology, warranting further study of GLP-1RA in MASLD management and its underlying mechanisms for better clinical decisions.