Mirjam Boros, Radcliffe Cardiology
A post hoc analysis of the SURPASS-CVOT trial suggests that tirzepatide, a dual GIP/GLP-1 receptor agonist, is associated with a lower incidence of a broad composite of cardiorenal events compared with the GLP-1 receptor agonist dulaglutide in patients with type 2 diabetes and established cardiovascular disease.¹
Tirzepatide is a dual agonist that targets both glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. The original SURPASS-CVOT trial demonstrated non-inferiority for tirzepatide versus dulaglutide for a 3-component composite of major adverse cardiovascular events (MACE). This new analysis expands on these findings by assessing a wider range of outcomes.
Methodology
This post hoc analysis used data from the SURPASS-CVOT (Study of Tirzepatide Compared With Dulaglutide on MACE in Participants With Type 2 Diabetes) trial, a parallel-design, double-blind, randomised clinical trial.¹˒² The study enrolled 13,165 patients with type 2 diabetes and established atherosclerotic cardiovascular disease.
Participants were randomised to receive weekly subcutaneous injections of either tirzepatide (escalated up to 15 mg) or a fixed dose of dulaglutide (1.5 mg). The primary efficacy measure for this analysis was the time to the first occurrence of a 6-component composite of cardiorenal outcomes, including all-cause mortality, myocardial infarction (MI), stroke, coronary revascularisation, hospitalisation for heart failure, and a composite of adverse kidney outcomes.
Results
After a median treatment duration of 46.9 months, the primary 6-component cardiorenal endpoint occurred in 1559 (23.7%) patients in the tirzepatide group compared with 1803 (27.4%) patients in the dulaglutide group (Hazard Ratio [HR] 0.84; 95% CI 0.79–0.90; p<0.001).¹
Each component contributed to the overall benefit. Notably, all-cause mortality occurred in 8.6% of the tirzepatide group versus 10.2% of the dulaglutide group (HR 0.84; 95% CI 0.75–0.94), and the composite kidney endpoint occurred in 4.9% versus 6.1%, respectively (HR 0.79; 95% CI 0.68–0.91).
Sensitivity analyses for a 5-component MACE endpoint (excluding kidney outcomes) and a 4-component MACE endpoint (excluding kidney and heart failure outcomes) showed consistent results (HR 0.86 for both). Gastrointestinal adverse events were more frequent with tirzepatide (42.5%) than with dulaglutide (35.9%).
In Practice
This analysis suggests that in patients with type 2 diabetes and high cardiovascular risk, the dual GIP/GLP-1 agonist tirzepatide was associated with a lower risk of a broad range of cardiorenal events compared to the GLP-1 agonist dulaglutide. The findings provide a more comprehensive comparison of the two incretin-based therapies on major sources of morbidity and mortality beyond the traditional 3-point MACE.
Next Steps
Further data on the effects of tirzepatide on cardiorenal outcomes, including all-cause mortality, are anticipated from the ongoing SURMOUNT-MMO trial, which is a large, placebo-controlled study in patients with obesity but without diabetes.
This study was funded by Eli Lilly and Company.
Disclaimer
The information presented in this article is for educational purposes only. Any quotes included reflect the opinions of the individual quoted, and do not necessarily reflect the views of the publisher. The publisher does not guarantee the accuracy or completeness of the content and accepts no responsibility for any errors, or any consequences arising from its use.
References
1. 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. 2026. https://doi.org/10.1001/jamacardio.2026.0767
2. Nicholls SJ, Bhatt DL, Buse JB, et al. Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS-CVOT design and baseline characteristics. Am Heart J. 2024;267:1-11. https://doi.org/10.1016/j.ahj.2023.09.007