Tirzepatide Lowers Cardiovascular and Kidney Events vs Dulaglutide in High-Risk Diabetes: Study

The incidence of major cardiovascular and kidney outcomes is reduced by tirzepatide compared to dulaglutide in patients with type 2 diabetes and cardiovascular disease. The cardiometabolic advantage of tirzepatide extends beyond glucose control. Cardiovascular and kidney complications are major causes of morbidity and mortality among patients with type 2 diabetes. Previous studies have shown the non-inferiority of tirzepatide compared to dulaglutide for major cardiovascular outcomes. The current post hoc analysis extends the scope of previous studies by assessing a wider composite of adverse cardiorenal outcomes.

This post hoc analysis was based on a large, double-blind, randomized clinical trial carried out in 640 centers in North and South America, Europe, Asia, and Oceania. The trial enrolled 13,165 patients with type 2 diabetes and pre-existing cardiovascular disease from May 29, 2020, to June 27, 2022, with analysis carried out from July 2025 to February 2026. The patients enrolled in this trial were 64 (±8.8) years of age on average, with 71.0% male (n=9,348) and 29.0% female (n=3,817). The mean baseline HbA1c levels were 8.4% (±0.93%), indicating suboptimal control.

Participants were randomly assigned to receive once-weekly subcutaneous injections of tirzepatide up to 15 mg (n=6,586) or dulaglutide 1.5 mg (n=6,579). Median treatment duration was 46.9 months (IQR 34.6–50.6), which is sufficient to evaluate the long-term outcome. The composite outcome included six major cardiorenal events, including all-cause death, myocardial infarction, stroke, coronary revascularization, hospitalization for heart failure, and adverse kidney outcomes. Other analyses included composite outcomes with narrower event sets excluding kidney and/or heart failure.

Key findings:

• A total of 13,165 patients were included in the analysis.

• The primary composite cardiorenal outcome was seen in 1,559 patients (23.7%) in the tirzepatide group compared with 1,803 patients (27.4%) in the dulaglutide group.

• Tirzepatide resulted in reduction with hazard ratio (HR) 0.84 (95% CI 0.79–0.90; p < 0.001).

• In the 5-component outcome excluding kidney outcomes, the HR was 0.86 (95% CI 0.80–0.93).

• In the 4-component outcome excluding kidney and heart failure outcomes, the HR again was 0.86 (95% CI 0.80–0.93).

• Gastrointestinal adverse events were seen in 2,827 patients (42.5%) receiving tirzepatide and 2,387 patients (35.9%) receiving dulaglutide.

Tirzepatide is shown to decrease the risk of major cardiovascular and kidney outcomes compared to dulaglutide in patients with type 2 diabetes and cardiovascular disease, which makes it a comprehensive cardiometabolic therapy.

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