Tirzepatide matches dulaglutide on heart events in four-year SURPASS-CVOT trial

The full results of the SURPASS-CVOT trial were published December 17, 2025, in the New England Journal of Medicine. The study found that tirzepatide (Mounjaro) was no worse than dulaglutide (Trulicity) at preventing cardiovascular death, heart attack or stroke in people who have type 2 diabetes and atherosclerotic cardiovascular disease, the narrowing of arteries that can cause heart attacks ^[1][4].

The trial randomly assigned 13,299 patients to weekly injections of tirzepatide (up to 15 mg) or dulaglutide (1.5 mg) ^[1]. After 134 people were excluded for not meeting entry criteria, the analysis included 6,586 patients on tirzepatide and 6,579 on dulaglutide, or 13,165 in total ^[1]. Median follow-up was four years ^[4]. The average age was 64.1 years, 29.0% were women, average body-mass index was 32.6, average A1c was 8.4%, and the average duration of diabetes was 14.7 years ^[1]. At enrollment, 81.4% were taking metformin, 48.8% insulin, 30.2% an SGLT2 inhibitor and 21.6% a sulfonylurea ^[4]. Eli Lilly, which makes both drugs, funded the trial, registered as NCT04255433 ^[1].

What the trial found

The main endpoint was a composite of cardiovascular death, heart attack or stroke. It occurred in 801 patients (12.2%) on tirzepatide and 862 (13.1%) on dulaglutide, a hazard ratio of 0.92 with a 95.3% confidence interval of 0.83 to 1.01. That met the trial's threshold for noninferiority (P=0.003) but not for superiority (P=0.09) ^[1]. An expanded measure that also counted coronary revascularization procedures was significantly lower with tirzepatide, hazard ratio 0.88, with a confidence interval that did not cross 1.0 ^[4]. All-cause death was less common on tirzepatide in an exploratory analysis, a difference the investigators said appeared to be driven by fewer noncardiovascular deaths ^[4].

On metabolic measures, tirzepatide produced larger weight loss than dulaglutide (-11.6% versus -4.5%) and larger A1c reductions (-1.66 versus -0.88 percentage points), along with greater declines in triglycerides ^[4].

For safety, gastrointestinal adverse events were more common on tirzepatide, 42.5% versus 35.9% ^[1]. Severe hypoglycemia was identical at 0.7% in each group, and adjudicated pancreatitis was identical at 0.6% in each group ^[1]. Investigator-reported acute kidney injury was 3.4% versus 2.7% ^[1]. Medullary thyroid cancer was reported in two tirzepatide patients, one of whose tumors carried a RET mutation ^[1]. Discontinuation because of adverse events was higher on tirzepatide, 13.2% versus 10.1%, largely driven by gastrointestinal effects ^[4].

"The take-home message is that this validates the cardiovascular benefit of tirzepatide," lead investigator Stephen Nicholls of the Victorian Heart Institute and Monash University in Australia told TCTMD. "We now have more evidence to use this agent in a range of clinical settings and, importantly, our patients have greater choice" ^[4]. Jaime Almandoz of UT Southwestern Medical Center, who was not involved in the study, said treatment decisions are likely to be guided less by expected differences in cardiovascular outcomes and more by weight loss, glucose control, tolerability and patient preference ^[4].

Why it matters for patients

This trial tested tirzepatide, not semaglutide. Ozempic, Wegovy and Rybelsus are all semaglutide, and no head-to-head cardiovascular comparison of tirzepatide with semaglutide is reported here ^[1][4].

Everyone in SURPASS-CVOT had type 2 diabetes plus established atherosclerotic cardiovascular disease, so the results describe that group rather than people using these medicines only for weight management ^[1]. Both treatment arms received an active drug, dulaglutide, which had already been shown to reduce cardiovascular events. That design means the trial shows tirzepatide is at least as good as dulaglutide on the main endpoint; it does not show tirzepatide is better, because the superiority test did not reach statistical significance ^[1][4].

For patients, the practical differences in this trial were metabolic and gastrointestinal: more weight loss and better glucose control on tirzepatide, but more stomach and bowel side effects and more people stopping treatment because of them ^[1][4].

What happens next

The top-line results were announced in the summer of 2025 and the trial was presented at the annual meeting of the European Association for the Study of Diabetes before publication ^[4]. Whether the Food and Drug Administration changes product labeling for tirzepatide based on these results has not been disclosed, and no timeline for guideline updates has been reported.