Tirzepatide significantly cut composite adverse outcomes by 34% compared to TZDs in MASLD patients

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disorder with significant morbidity. Both Tirzepatide (TZP) and thiazolidinediones (TZDs) have shown promise in managing MASLD and its metabolic comorbidities. However, direct comparative evidence on their real-world clinical effectiveness, especially regarding major adverse outcomes like cardiovascular events and mortality, has been scarce. This study addresses this critical gap by comparing these two treatment classes in a large patient cohort.

This retrospective, multi-institutional cohort study utilized data from the TriNetX global health research network. Researchers included adults with MASLD who were newly initiated on either Tirzepatide or thiazolidinediones. After 1:1 propensity score matching, each treatment arm comprised 9,262 patients. The primary outcome was a composite measure including 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.

Tirzepatide 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), representing a 34% lower risk.

Tirzepatide was linked to a 52% lower risk of all-cause mortality (HR, 0.48; 95% CI, 0.32-0.71) and a 50% lower risk of major adverse liver outcome (MALO) (HR, 0.50; 95% CI, 0.36-0.69). Additionally, major adverse cardiovascular events (MACE) were 35% lower (HR, 0.65; 95% CI, 0.51-0.82), and major adverse kidney events (MAKE) were 50% lower (HR, 0.50; 95% CI, 0.36-0.69). These beneficial associations remained consistent across subgroups stratified by age, sex, body mass index, and underlying comorbidities, suggesting broad applicability of these findings.