Cardiovascular outcomes with tirzepatide versus semaglutide in type 2 diabetes.
A large real-world propensity-matched cohort study (N=271,685 per arm) compared cardiovascular outcomes in patients with type 2 diabetes treated with tirzepatide versus semaglutide. Tirzepatide was associated with a significantly lower risk of a composite endpoint of acute myocardial infarction, stroke, and acute heart failure (HR 0.90; 95% CI 0.85–0.96) and reduced all-cause mortality (HR 0.80; 95% CI 0.74–0.84). While observational in design, these findings support the growing evidence that tirzepatide may offer superior cardioprotection compared to semaglutide in this population.
Objectives
tirzepatide is associated with greater glycemic control and weight reduction compared to semaglutide in patients with T2D. Tirzepatide has also been recently shown to be non-inferior to dulaglutide in cardiovascular risk reduction among patients with T2D. Whether tirzepatide is more or less effective than semaglutide for cardioprotection is underexplored.
Methods
The Research Collaborative Network of the TriNetX platform was accessed to collect de-identified, real world data on patients with T2D and compare the incidence of a composite of cardiovascular outcomes including acute myocardial infarction, stroke and acute heart failure, as well as all-cause mortality between patients who used tirzepatide and patients who used semaglutide during the period May 13, 2022 to Aug 11, 2026. One-to-one propensity score matching was applied to control for possible confounding covariates.
Results
two well-matched cohorts (N = 271,685 for each) were analyzed. Compared to the semaglutide group, the tirzepatide group had lower incidences of the primary composite outcome (4.6% vs. 5.5%; absolute risk difference [ARD] -0.9%, 95% confidence interval [CI] -1.01 to -0.77; hazard ratio [HR] 0.9, 95% CI 0.92─0.96) and all-cause mortality (0.6% vs. 0.9%; ARD - 0.3%, 95% CI -0.33 to -0.24; HR 0.8, 95% CI 0.74─0.84).
Conclusions
Tirzepatide was associated with lower risk of a composite of outcome of cardiovascular events as well as all-cause mortality compared to semaglutide in patients with T2D. CLINICAL TRIAL REGISTRATION: Clinical trial number: not applicable. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s40200-026-02087-z.
