Research Summary

Tirzepatide Associated With Fewer Cardiorenal Events in Type 2 Diabetes

Edited by:
Kate Young

Key Highlights:

  • In a post hoc analysis of 13,165 patients with type 2 diabetes and established cardiovascular disease, tirzepatide was associated with a lower rate of a 6-component cardiorenal composite outcome than dulaglutide.
  • The primary composite occurred in 23.7% of tirzepatide-treated patients versus 27.4% of dulaglutide-treated patients.
  • Gastrointestinal adverse events were more common with tirzepatide than dulaglutide.

In a post hoc analysis of the SURPASS-CVOT randomized clinical trial, published in JAMA Cardiology, tirzepatide was associated with a lower incidence of a broad composite of cardiovascular and kidney outcomes than dulaglutide in patients with type 2 diabetes and established cardiovascular disease. The analysis evaluated a 6-component composite that included all-cause mortality, myocardial infarction, stroke, coronary revascularization, hospitalization for heart failure, and adverse kidney outcomes.

The trial enrolled 13,165 patients across 640 centers in North and South America, Europe, Asia, and Australia. Mean age was 64 years, 71.0% of participants were male, and mean hemoglobin A1c was 8.4%. Patients were randomized to weekly subcutaneous tirzepatide up to 15 mg (n = 6,586) or dulaglutide 1.5 mg (n = 6,579). Enrollment ran from May 29, 2020, to June 27, 2022, and the post hoc analyses were conducted from July 2025 to February 2026.

SURPASS-CVOT was a randomized, double-blind, active-comparator global trial designed originally to test noninferiority of tirzepatide versus dulaglutide for a narrower 3-component major adverse cardiovascular event end point of cardiovascular death, myocardial infarction, or stroke. For this post hoc analysis, investigators expanded the efficacy assessment to a 6-component cardiorenal composite and analyzed time-to-event outcomes using a Cox proportional hazards model stratified by baseline sodium-glucose cotransporter 2 inhibitor use. No power calculations were performed for the broadened post hoc end point.

Study Findings

After a median treatment duration of 46.9 months, the 6-component cardiorenal end point occurred in 1,559 patients (23.7%) in the tirzepatide group and 1,803 patients (27.4%) in the dulaglutide group, corresponding to a hazard ratio of 0.84 (95% CI, 0.79-0.90; P < .001). Sensitivity analyses were directionally consistent: the 5-component composite excluding kidney outcomes yielded an HR of 0.86, and the 4-component composite excluding both kidney and heart failure outcomes also yielded an HR of 0.86. A version of the 6-component composite substituting cardiovascular death for all-cause mortality produced an HR of 0.85.

For individual components, all-cause mortality occurred in 8.6% of tirzepatide-treated patients and 10.2% of dulaglutide-treated patients (HR, 0.84; 95% CI, 0.75-0.94). Myocardial infarction occurred in 4.7% versus 5.4% (HR, 0.86; 95% CI, 0.74-1.00), stroke in 3.5% versus 3.8% (HR, 0.91; 95% CI, 0.76-1.09), coronary revascularization in 8.0% versus 9.4% (HR, 0.84; 95% CI, 0.75-0.95), heart failure hospitalization in 3.0% versus 3.1% (HR, 0.96; 95% CI, 0.79-1.17), and the composite kidney end point in 4.9% versus 6.1% (HR, 0.79; 95% CI, 0.68-0.91). Gastrointestinal adverse events were reported in 42.5% of patients treated with tirzepatide- and 35.9% of patients treated with dulaglutide.

Clinical Implications

According to the study authors, the findings suggest tirzepatide may be associated with fewer major cardiorenal adverse outcomes than dulaglutide in patients with type 2 diabetes and established cardiovascular disease when a broader composite outcome is considered. They also stated that the analysis provides a more comprehensive comparison of these incretin-based therapies across cardiovascular and kidney outcomes.

The authors noted several limitations. First, this was a secondary post hoc analysis of a trial built around a narrower primary end point, which could bias selection of components for the broader analysis. Second, the broader composite generated about twice as many events as the primary trial and therefore greater statistical power than originally intended; additionally, the trial included only patients at high cardiovascular risk, so similar results in lower-risk populations cannot be assumed.

Expert Commentary

“In this post hoc analysis of data for patients with type 2 diabetes and established cardiovascular disease, the dual GLP-1/GIP agonist tirzepatide, compared with the GLP-1 agonist dulaglutide was associated with a lower incidence of a broad 6-component cardiorenal end point that included all-cause mortality, myocardial infarction, stroke, coronary revascularization, heart failure, and adverse kidney outcomes,” the researchers concluded.

Reference
Nissen SE, Wolski K, D’Alessio D, et al. Cardiorenal outcomes with tirzepatide compared with dulaglutide in patients with diabetes and cardiovascular disease: a post hoc analysis of the SURPASS-CVOT randomized clinical trial. JAMA Cardiol. Published online March 28, 2026. doi:10.1001/jamacardio.2026.0767.