SURPASS-CVOT published: tirzepatide non-inferior to dulaglutide
Tirzepatide matched but did not beat dulaglutide on heart attacks, strokes and cardiovascular death in a 13,299-person trial, leaving the two drugs looking similar for heart protection.
Results from SURPASS-CVOT, a head-to-head cardiovascular outcomes trial of tirzepatide (sold as Mounjaro for type 2 diabetes and Zepbound for weight management) against the older GLP-1 drug dulaglutide, have been published in the New England Journal of Medicine. In adults with type 2 diabetes and atherosclerotic cardiovascular disease, tirzepatide met the trial's bar for non-inferiority but did not prove superior [1].
What the trial tested
The study was a double-blind, active-comparator trial: instead of comparing tirzepatide with a placebo, researchers compared it with dulaglutide 1.5 mg weekly, a drug already shown to lower the rate of cardiovascular events [1]. Participants were randomly assigned 1:1 to weekly injections of tirzepatide (up to 15 mg) or dulaglutide [1].
A total of 13,299 people were randomized, and 134 were later excluded because they did not meet entry criteria, leaving 6,586 in the tirzepatide group and 6,579 in the dulaglutide group in the main analysis [1]. On average, participants were 64.1 years old (standard deviation 8.8), 29.0% were women, mean body mass index was 32.6 (SD 5.5), mean A1C was 8.4% (SD 0.9), and they had lived with diabetes for a mean of 14.7 years (SD 8.8) [1].
The primary endpoint was a combination of death from cardiovascular causes, heart attack, or stroke [1]. The design called for non-inferiority if the upper limit of the 95.3% confidence interval for the hazard ratio stayed below 1.05; an upper limit below 1.00 would have shown superiority [1].
The numbers
A primary endpoint event occurred in 801 patients (12.2%) taking tirzepatide and 862 patients (13.1%) taking dulaglutide [1]. That works out to a hazard ratio of 0.92, with a 95.3% confidence interval of 0.83 to 1.01 [1]. The non-inferiority test was met (P = 0.003), but the superiority test was not (P = 0.09) [1].
In plain terms, the difference between the two groups was about 0.9 percentage points over the course of the trial, and the statistical range around that difference still includes the possibility of no benefit at all versus dulaglutide [1].
On safety, the overall rate of adverse events appeared similar between the groups, though more gastrointestinal side effects were seen with tirzepatide [1]. The published abstract does not break out specific rates of nausea, vomiting or diarrhea, and it does not report how much weight or A1C changed in each group, or how long participants were followed — those details are not available in the source material here [1].
The trial was funded by Eli Lilly, which makes both tirzepatide and dulaglutide, and is registered as NCT04255433 [1].
Why it matters for patients
For people with type 2 diabetes who also have clogged arteries, this trial answers a narrow but practical question: does switching to or starting the dual GIP/GLP-1 drug tirzepatide cost you heart protection compared with an established GLP-1 drug? Based on these results, the answer is no — tirzepatide performed at least as well as dulaglutide on the combined outcome of cardiovascular death, heart attack and stroke [1].
What the trial does not show is that tirzepatide is better for the heart than dulaglutide. The superiority test missed statistical significance [1]. That distinction matters for how doctors, guideline writers and insurers talk about the two drugs, and it may come up in conversations about formularies and prior authorization, though the study itself says nothing about coverage.
It also matters that this was an active-comparator trial. Because there was no placebo group, the study cannot quantify how much tirzepatide reduces cardiovascular risk compared with no GLP-1 therapy at all [1].
The gastrointestinal finding is consistent with what is already on tirzepatide labeling: more stomach-related side effects than the comparator, without an apparent increase in overall adverse events [1].
What happens next
The results have already drawn published debate. The New England Journal of Medicine ran five letters to the editor about the trial on April 16, 2026, along with a reply from the investigators, including correspondence from cardiology and stroke researchers [1]. Their specific critiques are not included in the source material available here.
Any changes to prescribing guidance or product labeling based on SURPASS-CVOT are not described in the source and are not yet known.
Sources
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