S2552 Semaglutide Versus Sodium-Glucose Cotransporter-2 Inhibitors for Liver and Cardiovascular Outcomes in Metabolic Dysfunction-Associated Fatty Liver Disease: A Propensity Score-Matched Cohort Study

Introduction: Semaglutide and SGLT2 inhibitors both reduce hepatic steatosis and improve key MAFLD outcomes, yet direct comparative data remain limited. Methods: We conducted a retrospective cohort study using de-identified TriNetX data to compare first‐time semaglutide versus SGLT2i use in MAFLD. Adults ≥18 years with an initial MAFLD diagnosis between January 1, 2018, and May 31, 2023, were included. The semaglutide group comprised patients with a first semaglutide prescription, and the comparator group comprised new SGLT2i users. We excluded patients with crossover exposure; baseline cirrhosis or other chronic liver diseases; alcohol use disorder; HIV infection; pregnancy within the prior year; or advanced CKD. Propensity score matching was used to balance baseline characteristics, and patients were followed for up to 2 years to assess cirrhosis and related outcomes. Results: After propensity-score matching (n = 584 per group; mean age 58.3 vs 58.2 years; 45.9% vs 46.4% man), semaglutide was associated with significant clinical benefits over time. At 6 months, semaglutide use was linked to a significantly lower risk of major adverse cardiovascular events (MACE) (RR 0.30, P < 0.001) and hospitalization (RR 0.46, P < 0.001), with no significant differences observed in decompensated cirrhosis (RR 0.83, P = 0.667) or non-alcohol-related cirrhosis (RR 0.87, P = 0.702). At 1 year, reductions in MACE and hospitalization persisted (RR 0.30, P < 0.001; RR 0.59, P = 0.002, respectively), while differences in all-cause mortality (RR 0.63, P = 0.234), decompensated cirrhosis (RR 0.77, P = 0.527), and non-alcohol-related cirrhosis (RR 1.11, P = 0.741) remained non-significant. By 2 years, semaglutide continued to confer a significantly lower risk of hospitalization (RR 0.63, P = 0.001) and MACE (RR 0.36, P < 0.001), while differences in all-cause mortality (RR 0.50, P = 0.064), decompensated cirrhosis (RR 0.77, P = 0.527), and non-alcohol-related cirrhosis (RR 0.86, P = 0.577) remained statistically non-significant. Conclusion: Semaglutide use in MAFLD patients was associated with sustained reductions in cardiovascular events and hospitalizations, though no significant differences were observed in cirrhosis-related outcomes compared to SGLT2 inhibitors.