Observational studyHepatology international2026
Efficacy of tirzepatide versus SGLT2 inhibitors in metabolic dysfunction-associated steatotic liver disease (MASLD): a multicenter propensity-matched real-world study.
Observational study in Hepatology international, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition with significant cardiometabolic and hepatic risks. Tirzepatide, a dual GLP-1/GIP receptor agonist, shows promise in MASLD, but real-world comparative data against sodium-glucose cotransporter-2 inhibitors (SGLT2is) are lacking.
methodsIn this multicenter, retrospective, propensity score-matched cohort study using the TriNetX US Collaborative Network, we compared outcomes in 43,743 new tirzepatide initiators versus 43,743 matched SGLT2i users with MASLD and ≥ 1 metabolic comorbidity. Propensity Score Matching (1:1, caliper 0.1) balanced > 50 covariates. Primary outcomes included all-cause mortality, hospitalization, major adverse cardiovascular events (MACE), major adverse liver outcomes (MALO), and major adverse kidney events (MAKE) at 1- and 3-year follow-up, analyzed via Kaplan-Meier estimation and Cox proportional hazards models.
resultsTirzepatide was associated with significantly lower risks versus SGLT2is. At 1-year follow-up (n = 43,743 per group), all-cause mortality events were 144 (cumulative incidence 0.48%, KM event-free survival 99.52%) with tirzepatide versus 533 (1.38%, 98.62%) with SGLT2i (HR 0.328, 95% CI 0.272-0.394; log-rank p < 0.0001). All-cause hospitalization occurred in 3033 versus 7143 (HR 0.460, 95% CI 0.441-0.480). MACE events were 1064 versus 2376 (HR 0.506, 95%CI 0.471-0.544). MALO events were 149 versus 465 (HR 0.379, 95% CI 0.315-0.456). Hepatic failure and ascites also favored tirzepatide, while MAKE, varices, and hepatic encephalopathy showed no significant differences. Benefits persisted at 3 years (n = 39,838 per group): mortality 208 versus 963 (HR 0.374, 95% CI 0.321-0.436); hospitalization 3723 versus 9548 (HR 0.528, 95%CI 0.508-0.549); MACE 1260 versus 3282 (HR 0.545, 95%CI 0.510-0.582); and MALO 220 versus 726 (HR 0.478, 95%CI 0.410-0.558).
conclusionsIn this large real-world MASLD cohort, tirzepatide was associated with substantial reductions in mortality, hospitalizations, cardiovascular, and liver-related events compared to SGLT2is. These observational findings suggest potential advantages of tirzepatide and warrant prospective validation in randomized trials.
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