Tirzepatide reduced a 6-component composite cardiorenal outcome compared with dulaglutide in patients with diabetes and cardiovascular disease (HR 0.84; 95% CI 0.79-0.90; P<0.001).
RCT (n=13,165)
Double-blind
parallel-design
Yes
Does subcutaneous tirzepatide reduce a broad composite of cardiorenal adverse outcomes compared to dulaglutide in patients with type 2 diabetes and cardiovascular disease?
In a post hoc analysis of a randomized trial, tirzepatide significantly reduced the risk of a broad composite of cardiovascular and kidney outcomes compared to dulaglutide in patients with type 2 diabetes and established cardiovascular disease.
Effect estimate: HR 0.84 (95% CI 0.79-0.90)
Absolute Event Rate: 23.7% vs 27.4%
p-value: p=<0.001
Importance The dual glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) agonist tirzepatide was noninferior to a GLP-1 agonist, dulaglutide, for effects on the composite outcome of cardiovascular death, myocardial infarction (MI), or stroke. However, comparison for a comprehensive range of major adverse cardiovascular and kidney outcomes has not been reported. Objective To perform a post hoc analysis for an expanded range of adverse outcomes in a completed randomized clinical trial comparing the effects of tirzepatide and dulaglutide in patients with type 2 diabetes and cardiovascular disease. Design, Setting, and Participants This parallel-design double-blind trial enrolled patients with diabetes and preexisting cardiovascular disease (from May 29, 2020, to June 27, 2022) at 640 centers in North and South America, Europe, Asia, and Oceania. Data were analyzed from July 2025 to February 2026. Interventions Participants were randomized to receive subcutaneous tirzepatide up to 15 mg (n = 6586) or a fixed dose of dulaglutide, 1.5 mg (n = 6579), administered weekly. Main Outcomes and Measures The primary efficacy measure was time from randomization to first occurrence of a 6-component composite of cardiorenal adverse outcomes, including all-cause mortality, MI, stroke, coronary revascularization, hospitalization for heart failure, and a composite of adverse kidney outcomes. Results Among the 13 165 patients enrolled, the mean (SD) age was 64 (8.8) years; 9348 patients (71.0%) were male and 3817 were female (29.0%). The mean (SD) hemoglobin A 1c was 8.4% (0.93). After a median (IQR) treatment duration of 46.9 (34.6-50.6) months, the primary cardiorenal end point occurred in 1559 tirzepatide-treated patients (23.7%) and 1803 dulaglutide-treated patients (27.4%; hazard ratio HR, 0.84; 95% CI, 0.79-0.90; P lt; .001). Sensitivity analyses showed similar hazard ratios for a narrower 5-component end point (without the kidney composite outcomes: HR, 0.86; 95% CI, 0.80-0.93) and the 4-component composite (without either kidney or heart failure end points: HR, 0.86; 95% CI, 0.80-0.93). Gastrointestinal adverse events were more common with tirzepatide (2827 patients 42.5%) than dulaglutide (2387 patients 35.9%) treatment. Other adverse events were similar. Conclusions In this post hoc analysis, the dual GLP-1 and GIP agonist tirzepatide, compared with the GLP-1 agonist dulaglutide, was associated with a lower incidence of a broad 6-component composite cardiovascular and kidney end point in patients with diabetes and established cardiovascular disease. Trial Registration ClinicalTrials.gov Identifier: NCT04255433
This post-hoc analysis of the SURPASS-CVOT trial, showing tirzepatide's superiority over dulaglutide in reducing a broad range of cardiorenal events, is driving significant discussion following its presentation at ACC 2026 and recent FDA approval for cardiovascular risk reduction.
NISSEN et al. (2026) conducted an RCT in type 2 diabetes and cardiovascular disease (n=13,165). tirzepatide vs. dulaglutide 1.5 mg weekly was evaluated on 6-component composite of cardiorenal adverse outcomes (all-cause mortality, MI, stroke, coronary revascularization, hospitalization for heart failure, and adverse kidney outcomes) (HR 0.84, 95% CI 0.79-0.90, p=<0.001). Tirzepatide reduced a 6-component composite cardiorenal outcome compared with dulaglutide in patients with diabetes and cardiovascular disease (HR 0.84; 95% CI 0.79-0.90; P<0.001).