P3638 - 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

Ahmed Abuhasna, DO¹, Abdalhakim Shubietah, MD¹, Maysam Tawba, MCP², Islam Rajab, MD³, Abdallah Hussein, MD⁴, Mohammad Ghannam, MD⁵, Qutaiba Qafisheh, MD⁶, Mohammad Alqadi, MD⁶, Muath A. Baniowda, MD⁷, Omar Hamadi, MD¹
1Advocate Illinois Masonic Medical Center, Chicago, IL; 2Al Qassimi Women's and Children's Hospital, Sharjah, Sharjah, United Arab Emirates; 3St. Joseph's University Medical Center, Paterson, NJ; 4Virtua Our Lady of Lourdes Hospital, Camden, NJ; 5Brookdale University Hospital Medical Center, New York, NY; 6University of Toledo, Toledo, OH; 7University of Missouri Kansas City School of Medicine, Kansas City, MO

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 two 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% male), 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.

Discussion: 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.

Disclosures:
Ahmed Abuhasna indicated no relevant financial relationships.
Abdalhakim Shubietah indicated no relevant financial relationships.
Maysam Tawba indicated no relevant financial relationships.
Islam Rajab indicated no relevant financial relationships.
Abdallah Hussein indicated no relevant financial relationships.
Mohammad Ghannam indicated no relevant financial relationships.
Qutaiba Qafisheh indicated no relevant financial relationships.
Mohammad Alqadi indicated no relevant financial relationships.
Muath A. Baniowda indicated no relevant financial relationships.
Omar Hamadi indicated no relevant financial relationships.

Ahmed Abuhasna, DO¹, Abdalhakim Shubietah, MD¹, Maysam Tawba, MCP², Islam Rajab, MD³, Abdallah Hussein, MD⁴, Mohammad Ghannam, MD⁵, Qutaiba Qafisheh, MD⁶, Mohammad Alqadi, MD⁶, Muath A. Baniowda, MD⁷, Omar Hamadi, MD¹. P3638 - 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, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.