Summary: In the large SURPASS-CVOT trial in type 2 diabetes with established cardiovascular disease, tirzepatide was noninferior, but not superior, to dulaglutide for major adverse cardiovascular events, confirming that both incretin therapies are cardioprotective.
PICO Summary
| Element | Detail |
|---|---|
| Population | 13,165 patients with type 2 diabetes and atherosclerotic cardiovascular disease (mean age 64; HbA1c 8.4%); active-comparator, double-blind, noninferiority trial. |
| Intervention | Once-weekly tirzepatide up to 15 mg (n=6586). |
| Comparison | Once-weekly dulaglutide 1.5 mg (n=6579), an agent with proven cardiovascular benefit. |
| Outcome | A primary event (cardiovascular death, myocardial infarction, or stroke) occurred in 12.2% on tirzepatide versus 13.1% on dulaglutide (HR 0.92; 95.3% CI 0.83–1.01; p=0.003 for noninferiority; p=0.09 for superiority). Adverse events were broadly similar, though gastrointestinal events were more frequent with tirzepatide. |
SURPASS-CVOT
RCT · type 2 diabetes with ASCVD · noninferiority
Tirzepatide was noninferior but not superior to dulaglutide for major cardiovascular events. Both incretin therapies remain cardioprotective; tirzepatide's advantage lies in glucose and weight, not the heart.
Expert Commentary
This is an important landmark trial, and its result should be stated with precision: tirzepatide met noninferiority but did not achieve superiority over dulaglutide for major cardiovascular events, with a hazard ratio of 0.92 whose confidence interval crossed 1.0 and a superiority p-value of 0.09. The clinically reassuring message is that adding GIP agonism to GLP-1 agonism does not compromise cardiovascular protection, answering a genuine mechanistic question, and the active-comparator design against an agent with proven benefit sets a higher evidential bar than placebo-controlled trials. What the trial does not support is the marketing-friendly idea that tirzepatide beats dulaglutide for the heart; on these data the two are cardiovascularly comparable, and tirzepatide’s edge lies in glycaemic control and weight, at the cost of more gastrointestinal effects. Limitations include the unestablished superiority leaving open whether a longer or differently powered trial would separate them, and possible differential discontinuation from gastrointestinal events. Can I use this with my patients? Yes, to choose on the right grounds. For a patient with established cardiovascular disease, both agents protect the heart, so I would select tirzepatide where greater weight loss and glucose lowering are priorities and tolerability allows, and retain dulaglutide for those doing well or sensitive to gastrointestinal effects, rather than implying one is cardioprotectively superior.
References
Nicholls SJ, Pavo I, Bhatt DL, et al. Cardiovascular outcomes with tirzepatide versus dulaglutide in type 2 diabetes. N Engl J Med. 2025;393(24):2409–2420. doi:10.1056/NEJMoa2505928