Mounjaro matches Trulicity on heart risk in first head-to-head trial

Eli Lilly said on July 31, 2025 that Mounjaro (tirzepatide) was non-inferior to Trulicity (dulaglutide) for preventing cardiovascular death, heart attack or stroke, in the first large trial to compare two incretin medicines head-to-head rather than against a placebo ^[1][4].

SURPASS-CVOT enrolled 13,299 adults with type 2 diabetes and established atherosclerotic cardiovascular disease at 640 sites in 30 countries, and ran about five years, with a median follow-up of four years ^[1][2]. Participants were randomly assigned to weekly Mounjaro at the maximum tolerated dose of 5, 10 or 15 mg, or to Trulicity 1.5 mg ^[1]. The primary endpoint was MACE-3, a composite of cardiovascular death, heart attack or stroke ^[1][2].

The MACE-3 rate was 8% lower with Mounjaro than with Trulicity (hazard ratio 0.92; 95.3% CI 0.83 to 1.01), meeting the prespecified non-inferiority bar of an upper confidence limit below 1.05 ^[1][3]. Superiority was not established, Lilly and the FDA both said ^[2].

Other results, which were not adjusted for multiple comparisons, included a 16% lower rate of death from any cause with Mounjaro (hazard ratio 0.84; 95.0% CI 0.75 to 0.94) ^[1]. Among participants at high or very high risk of chronic kidney disease, Mounjaro slowed the decline in eGFR by 3.54 mL/min/1.73 m2 at 36 months compared with Trulicity (95.0% CI 2.57 to 4.50) ^[1][3]. Average A1C fell 1.73 percentage points with Mounjaro and 0.90 points with Trulicity, from a group mean of 8.39%; body weight fell 12.06% and 4.95% respectively, from a mean of 92.6 kg (204.15 lbs) ^[1][3].

A prespecified indirect comparison of matched patient data from SURPASS-CVOT and the 2019 REWIND trial of Trulicity estimated that Mounjaro cut MACE-3 by 28% and all-cause death by 39% against what the company called a "putative placebo" ^[1]. That calculation borrows data from a separate study, so it is an estimate rather than a direct comparison; the FDA approval rests on the head-to-head numbers ^[2].

Digestive side effects were the most common in both groups, generally mild to moderate, and mostly resolved once dose increases were finished ^[1]. In the trial, 13.3% of Mounjaro participants and 10.2% of Trulicity participants stopped treatment because of adverse events ^[1][5].

Why it matters for patients

The study population — adults with type 2 diabetes who already had atherosclerotic cardiovascular disease — is a group at high risk of heart attack or stroke. A placebo-controlled trial can show that a drug beats nothing; this one asked whether tirzepatide preserves a heart benefit that dulaglutide had already shown against placebo, and it did ^[1][2]. The two drugs looked comparable on that endpoint, and the trial was not designed to prove one better than the other ^[2].

Group averages do not predict what will happen to one person. The trial compared tirzepatide with dulaglutide, not with semaglutide (Ozempic, Wegovy, Rybelsus) or any other GLP-1 medicine ^[1].

On August 28, 2026, the FDA approved Mounjaro to lower the risk of major cardiovascular events — cardiovascular death, non-fatal heart attack or non-fatal stroke — in adults with type 2 diabetes who are at high risk for those events ^[2]. The label covers adults at high risk, a broader group than the trial's participants, who all had established disease ^[1][2]. Mounjaro was already approved to improve blood sugar in adults and children 10 and older ^[2].

What happens next

Full SURPASS-CVOT results were presented at the European Association for the Study of Diabetes annual meeting in September 2025 and published in the New England Journal of Medicine ^[1][2]. Data from the trial have been included in Mounjaro's product information in the European Union, and regulatory submissions based on the trial are under review in additional markets, Lilly said ^[2].

A separate trial, SURMOUNT-MMO, is testing tirzepatide in people with overweight and established cardiovascular disease or multiple risk factors; results are not expected until 2027 ^[4].