Efficacy of Tirzepatide Versus SGLT2 Inhibitors in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): a Multicenter Propensity-Matched Real-World Study

Metabolic 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. In 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. Tirzepatide 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