Tirzepatide Lowers Cardiovascular and Kidney Events vs Dulaglutide in High-Risk Diabetes: Study
In a new post hoc analysis, tirzepatide was associated with a lower incidence of a composite cardiovascular and kidney outcome compared with Dulaglutide in patients with diabetes and established cardiovascular disease, suggesting superior cardiorenal benefit in this high-risk population. The study was published in JAMA Cardiology by Steven E. and colleagues.
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
