Comparative effectiveness of tirzepatide versus thiazolidinedione in adults with MASLD: a propensity score-matched cohort study.

BACKGROUND: Tirzepatide (TZP) and thiazolidinediones (TZDs) have both shown promise in treating metabolic dysfunction-associated steatotic liver disease (MASLD), yet direct comparative evidence remains scarce. This real-world study aimed to compare the clinical effectiveness of TZP and TZDs in adults diagnosed with MASLD. METHODS: We conducted a retrospective, multi-institutional cohort study using data from the TriNetX global health research network. Adults with MASLD who were newly initiated on TZP or TZD were included. The primary outcome was a composite measure encompassing all-cause mortality, major adverse liver outcome (MALO), major adverse cardiovascular event (MACE), and major adverse kidney event (MAKE). Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards models. RESULTS: After 1:1 propensity score matching, each treatment arm included 9,262 patients. TZP use was significantly associated with a reduced risk of the composite primary outcome compared to TZD (HR, 0.66; 95% CI, 0.58-0.42). Additionally, TZP was linked to lower risks of all-cause mortality (HR, 0.48; 95% CI, 0.32-0.71), MALO (HR, 0.50; 95% CI, 0.36-0.69), MACE (HR, 0.65; 95% CI, 0.51-0.82), and MAKE (HR, 0.50; 95% CI, 0.36-0.69). These associations were consistent across subgroups stratified by age, sex, body mass index, and underlying comorbidities. CONCLUSION: In this large real-world cohort study, TZP was associated with lower risks of all-cause mortality, MALO, MACE, and MAKE compared to TZDs in adults with MASLD. While these findings suggest a potential clinical advantage, the observational design precludes causal inference. Prospective randomized trials are needed to confirm these associations and establish evidence-based treatment recommendations.