Efficacy of Initiation of Semaglutide versus SGLT2 inhibitors in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Multicenter Propensity-Matched Real-World Study.
Publication/Presentation Date
6-19-2026
Abstract
OBJECTIVES: Metabolic dysfunction-associated steatotic liver disease (MASLD) is common and linked to cardiometabolic comorbidities, with few direct comparisons between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is).
METHODS: This multicenter, retrospective, propensity score-matched cohort study utilized data from the TriNetX U.S. Collaborative Network. Adults with MASLD and at least one metabolic comorbidity were identified as new initiators of semaglutide (n=128,332) or SGLT2is (n=100,542), excluding alternative exposures and confounding liver etiologies. One-to-one propensity score matching on >50 covariates yielded balanced cohorts of 55,525 patients each. Time-to-event outcomes, including all-cause mortality, hospitalization, major adverse cardiovascular events (MACE), major adverse liver outcomes (MALO), major adverse kidney events (MAKE), ascites, hepatic failure, and hepatic encephalopathy, were evaluated at 1-year and 5-year follow-ups using Kaplan-Meier analysis and Cox proportional hazards models.
RESULTS: Semaglutide was linked to significant risk reductions compared to SGLT2is. At 1-year, hazard ratios (HRs) were 0.382 (95% CI 0.338-0.430) for all-cause mortality, 0.444 (95% CI 0.429-0.459) for all-cause hospitalization, 0.502 (95% CI 0.476-0.530) for MACE, and 0.361 (95% CI 0.316-0.412) for MALO. At 5-years, the corresponding HRs were 0.494 (95% CI 0.459-0.531), 0.565 (95% CI 0.551-0.579), 0.584 (95% CI 0.560-0.609), and 0.494 (95% CI 0.452-0.540). MAKE showed no difference at 1-year (HR 0.998), but a reduction at 5-years (HR 0.858; 95% CI 0.789-0.933). Individual liver events (ascites, hepatic failure) followed similar patterns.
CONCLUSIONS: In this large real-world MASLD cohort, initiating semaglutide was linked to potential reductions in mortality, hospitalization, and adverse cardiometabolic, liver, and kidney outcomes compared to SGLT2is.
ISSN
1530-891X
Published In/Presented At
Khalil, I., Sarker, P., Hossain, M. I., Chowdhury, A., Anwar Khalid, A., Saha, A., Chowdhury, J., Akter, M. M., Promi, S. A., Sayed, M. A., Rahman, M. T., & Kamrul-Hasan, A. B. M. (2026). Efficacy of Initiation of Semaglutide versus SGLT2 inhibitors in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Multicenter Propensity-Matched Real-World Study. Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists, S1530-891X(26)01038-4. Advance online publication. https://doi.org/10.1016/j.eprac.2026.06.004
Disciplines
Medicine and Health Sciences
PubMedID
42320716
Department(s)
Fellows and Residents
Document Type
Article