Tirzepatide significantly cut all-cause mortality and MACE in MASLD patients versus SGLT2 inhibitors

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent condition carrying substantial cardiometabolic and hepatic risks, yet effective pharmacological treatments remain limited. Current standard-of-care often involves lifestyle modifications, but there's a critical need for therapies that address both the liver pathology and associated comorbidities. Tirzepatide, a dual GLP-1/GIP receptor agonist, and SGLT2 inhibitors (SGLT2is) have shown promise in improving metabolic health, but real-world comparative data on their efficacy in MASLD patients, particularly regarding hard clinical endpoints, has been lacking.

This multicenter, retrospective, propensity score-matched cohort study utilized the TriNetX US Collaborative Network to compare outcomes. Researchers analyzed 43,743 new tirzepatide initiators against 43,743 matched SGLT2i users, all diagnosed with MASLD and at least one metabolic comorbidity. Propensity Score Matching (1:1, caliper 0.1) was employed to balance over 50 covariates between the groups. 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-ups, analyzed using Kaplan-Meier estimation and Cox proportional hazards models.

Tirzepatide was associated with significantly lower risks across multiple endpoints compared to SGLT2is. At 1-year follow-up (n=43,743 per group): all-cause mortality events were 144 (cumulative incidence 0.48%) with tirzepatide versus 533 (1.38%) 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. MAKE, varices, and hepatic encephalopathy showed no significant differences. Benefits persisted at 3 years (n=39,838 per group):

All-cause mortality was 208 with tirzepatide versus 963 with SGLT2i (HR 0.374, 95% CI 0.321-0.436). Hospitalization was 3723 versus 9548 (HR 0.528, 95% CI 0.508-0.549); MACE was 1260 versus 3282 (HR 0.545, 95% CI 0.510-0.582); and MALO was 220 versus 726 (HR 0.478, 95% CI 0.410-0.558).