Efficacy of Initiation of Semaglutide versus SGLT2 inhibitors in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Multicenter Propensity-Matched Real-World Study.

Authors

• Ibrahim Khalil
• Pallab Sarker, Department of Medicine, Division of Internal Medicine, Reading Hospital - Tower Health, West Reading, PAFollow
• Md Imran Hossain
• Anika Chowdhury
• Aizaz Anwar Khalid
• Ananna Saha
• Joydip Chowdhury
• Mst Mahmuda AkterFollow
• Sunjida Amin Promi
• Md Abu Sayed
• Mohd Turzo Rahman
• A B M Kamrul-Hasan

Document Type

Article

Publication 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.

Publication Title

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

Comments

Online ahead of print.

Recommended Citation

Khalil, I., Sarker, P., Hossain, M., Chowdhury, A., Anwar Khalid, A., Saha, A., Chowdhury, J., Akter, M., Promi, S., Sayed, M., Rahman, M., & Kamrul-Hasan, A. (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 https://doi.org/https://doi.org/10.1016/j.eprac.2026.06.004