Tirzepatide Outperforms Dulaglutide on Cardiorenal Outcomes in High-Risk Diabetes

Tirzepatide (Mounjaro; Eli Lilly), a dual glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist, offers broader cardiorenal protection than dulaglutide, a GLP-1 receptor agonist, in patients with type 2 diabetes and established cardiovascular disease (CVD), according to new findings.¹

This post hoc analysis is published in JAMA Cardiology.

“The current post hoc analysis was undertaken to evaluate the association of tirzepatide and dulaglutide with outcomes for an expanded 6-component composite cardiorenal end point that included all-cause mortality, MI [myocardial infarction], stroke, coronary revascularization, heart failure, and serious adverse kidney outcomes,” wrote the researchers of the study.

SURPASS-CVOT (NCT04255433) is a randomized, double-blind cardiovascular outcomes trial evaluating the safety and efficacy of tirzepatide vs dulaglutide in 13,299 patients with type 2 diabetes and established atherosclerotic CVD across 640 sites in 30 countries.² The primary end point was time to first major adverse cardiovascular event (MACE): cardiovascular death, MI, or stroke.

In the analysis, patients were enrolled between May 2020 and June 2022 and randomized to receive either subcutaneous tirzepatide, titrated up to 15 mg weekly (n = 6586), or a fixed dose of dulaglutide at 1.5 mg weekly (n = 6579).¹ The mean (SD) patient age was 64 (8.8) years, 71% were male, and the mean hemoglobin A_1C was 8.4% (0.93%) at baseline—reflecting a population with poorly controlled diabetes and high cardiovascular risk. Data were analyzed from July 2025 through February 2026.

After a median (IQR) treatment duration of nearly 47 (34.6-50.6) months, the primary cardiorenal composite end point occurred in 23.7% of tirzepatide-treated patients compared with 27.4% of those receiving dulaglutide—a statistically significant difference (HR, 0.84; 95% CI, 0.79-0.90; P < .001).

The benefit was held across multiple sensitivity analyses. A narrower 5-component end point, which excluded the kidney composite, yielded a similar result (HR, 0.86; 95% CI, 0.80-0.93), as did a 4-component composite that excluded heart failure hospitalization (HR, 0.86; 95% CI, 0.80-0.93). This consistency across end point configurations strengthened confidence that the cardiorenal benefit of tirzepatide is robust and not driven by any single outcome component.

However, the researchers noted limitations on their results. As a post hoc analysis, the study is subject to potential bias in outcome component selection, though each was prespecified and most were centrally adjudicated. The expanded end point roughly doubled the number of events, generating greater statistical power than the original trial intended. Additionally, enrollment was restricted to patients with established CVD, limiting generalizability to lower-risk populations with type 2 diabetes. Whether tirzepatide can confer similar cardiorenal benefits in broader patient groups remains unknown.

Despite these limitations, for clinicians managing patients with type 2 diabetes and established CVD, these data suggest that tirzepatide may offer meaningful advantages over dulaglutide in glycemic control and in reducing the risk of a broad range of adverse cardiovascular and kidney outcomes—a finding with potentially significant implications for treatment selection in this high-risk population.

“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, MI, stroke, coronary revascularization, heart failure, and adverse kidney outcomes,” concluded the researchers.

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. Published online March 28, 2026. doi: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. doi:10.1016/j.ahj.2023.09.007