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Randomized controlled trial

SURPASS-CVOT: tirzepatide vs dulaglutide and heart outcomes

Over a median follow-up of 4.0 years, a major cardiovascular event occurred in 12.2% of patients on tirzepatide and 13.1% on dulaglutide (hazard ratio 0.92; 95.3% CI, 0.83 to 1.01).

Nicholls SJ et al. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. New England Journal of Medicine, 2025. DOI: 10.1056/NEJMoa2505928

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Key facts

Drugs
tirzepatide and dulaglutide
Design
Randomized controlled trial
Participants
13,299
Duration
Event-driven (follow-up is given in the results)
Funding
Eli Lilly
Registry
NCT04255433
Population
13,299 adults aged 40 or older with type 2 diabetes and atherosclerotic cardiovascular disease (HbA1c of 7 to 10.5% and BMI of 25 or more), at 640 sites in 30 countries; 13,165 were analyzed (mean age 64.1 years, 29.0% women, mean BMI 32.6, mean HbA1c 8.4% and an average of 14.7 years with diabetes).
Primary outcome
First major cardiovascular event (cardiovascular death, heart attack or stroke) with tirzepatide (up to 15 mg once weekly) versus dulaglutide 1.5 mg once weekly, with a primary noninferiority hypothesis.

What it found

Over a median follow-up of 4.0 years, a major cardiovascular event occurred in 12.2% of patients on tirzepatide and 13.1% on dulaglutide (hazard ratio 0.92; 95.3% CI, 0.83 to 1.01). Tirzepatide was noninferior to dulaglutide (p = 0.003), but the difference did not reach statistical significance for superiority (p = 0.09). The incidence of adverse effects was similar in both groups, with more digestive effects on tirzepatide.

Limitations

Funded by Eli Lilly, which makes both tirzepatide and dulaglutide. It compared tirzepatide with dulaglutide, a drug already shown to reduce cardiovascular events, and not with placebo, so it does not measure the effect of tirzepatide versus receiving neither drug. It only included people with type 2 diabetes and established cardiovascular disease.

What it means for you

In people with type 2 diabetes and cardiovascular disease, tirzepatide was no worse than dulaglutide (Trulicity) at preventing heart attacks, strokes and cardiovascular deaths, but it was not shown to be better either. The comparison was with another active drug, not with placebo. If you have diabetes and a history of heart disease, it is a useful finding to discuss with your doctor.

Further reading

Related trials

  • tirzepatide and semaglutide40 weeks

    SURPASS-2

    HbA1c fell by 2.01, 2.24 and 2.30 percentage points with tirzepatide 5, 10 and 15 mg, compared with 1.86 points with semaglutide 1 mg.

  • tirzepatide52 weeks

    SURPASS-3

    At 52 weeks, HbA1c fell by 1.93, 2.20 and 2.37 percentage points with tirzepatide 5, 10 and 15 mg, and by 1.34 points with insulin degludec.

  • tirzepatide88 weeks

    SURMOUNT-4 (post hoc analysis)

    After switching from tirzepatide to placebo, the more weight people regained between week 36 and week 88, the more their cardiometabolic parameters worsened: waist circumference increased by 0.8 cm in those who regained less than 25% of the weight lost and by 14.7 cm in those who regained 75% or more.

  • tirzepatide112 weeks

    SURMOUNT-MAINTAIN

    At week 112, weight had changed by −21.9% on the maximum tolerated dose of tirzepatide, −16.6% on 5 mg and −9.9% on placebo.

Sources

The original paper and the records consulted for this summary, with the date they were accessed.

  1. New England Journal of Medicine.Nicholls SJ, et al. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes. N Engl J Med. 2025;393(24):2409-2420.accessed .
  2. National Library of Medicine (PubMed).PubMed record PMID 41406444 (abstract).accessed .
  3. The Lancet Diabetes & Endocrinology.Zoungas S, et al. Tirzepatide and dulaglutide on major kidney events: pre-specified exploratory analyses of the SURPASS-CVOT trial. Lancet Diabetes Endocrinol. 2026;14(7):544-557 (sites, eligibility and median follow-up; PMID 42114520).accessed .