SURPASS-CVOT published in the New England Journal of Medicine

The full results of SURPASS-CVOT, the large cardiovascular outcomes trial of tirzepatide (sold as Mounjaro for type 2 diabetes and Zepbound for obesity), were published in the New England Journal of Medicine. In people with type 2 diabetes and established atherosclerotic cardiovascular disease, tirzepatide was found to be non-inferior to dulaglutide — another weekly injected GLP-1 drug already shown to reduce cardiovascular events — but it did not prove superior ^[1].

What the trial measured

SURPASS-CVOT was a double-blind, active-comparator trial funded by Eli Lilly (ClinicalTrials.gov number NCT04255433) ^[1]. Participants were randomly assigned 1:1 to a weekly injection of tirzepatide (up to 15 mg) or dulaglutide (1.5 mg) ^[1]. Unlike many drug trials, there was no placebo group: everyone received an active medication known to have cardiovascular benefit ^[1].

A total of 13,299 patients were randomized, and 134 were later excluded because they did not meet the inclusion criteria, leaving 6,586 patients in the tirzepatide group and 6,579 in the dulaglutide group ^[1]. The average age was 64.1 years, 29.0% were women, the average body-mass index was 32.6, the average glycated hemoglobin (A1C) was 8.4%, and participants had lived with diabetes for an average of 14.7 years ^[1].

The primary endpoint was a combined measure of death from cardiovascular causes, heart attack, or stroke ^[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 trial was designed so that tirzepatide would be declared non-inferior if the upper end of that confidence interval stayed below 1.05, and superior if it fell below 1.00 ^[1]. The upper bound landed at 1.01. So the non-inferiority test was met (P = 0.003), while the superiority test was not (P = 0.09) ^[1].

In plain terms: tirzepatide did not do worse than a drug with proven heart benefits, and the numbers trended slightly in its favor, but the trial could not rule out that the difference was due to chance.

On safety, the overall rate of adverse events appeared similar between the two groups, though more gastrointestinal adverse events were seen with tirzepatide ^[1]. The published abstract does not break out specific rates of nausea, vomiting or diarrhea, so those details are not available from this source.

Why it matters for patients

Many people with type 2 diabetes and heart disease take a GLP-1 drug partly for cardiovascular protection, not just for blood sugar or weight. Until now, tirzepatide — which acts on both the GLP-1 and GIP receptors — did not have a completed cardiovascular outcomes trial, and its effect on heart events was described by the authors as uncertain ^[1].

This publication changes that picture in a specific, limited way. It provides evidence that tirzepatide is at least as good as dulaglutide for preventing cardiovascular death, heart attack and stroke in this population ^[1]. It does not establish that tirzepatide is better, and because the comparison was against an active drug rather than placebo, the trial was not designed to measure how much benefit tirzepatide provides compared with no GLP-1 treatment at all.

It also does not answer questions about people without type 2 diabetes or without existing heart disease. The trial enrolled only patients who had both ^[1].

The gastrointestinal finding is consistent with what is already known about this drug class, but people weighing options with a clinician may want to know that in a head-to-head comparison, stomach-related side effects were more common on tirzepatide than on dulaglutide ^[1].

What happens next

The results are now in the peer-reviewed literature and available for medical societies and regulators to review. Whether the FDA adds any cardiovascular language to tirzepatide labeling based on this trial is not addressed in the published paper.

The New England Journal of Medicine subsequently published a set of correspondence letters about the trial on April 16, 2026, along with a reply from the investigators, indicating continued debate among cardiologists and diabetes specialists about how to interpret the near-miss on superiority ^[1].