Lilly says Mounjaro matched Trulicity on heart events and cut all-cause deaths in large trial

Eli Lilly said July 31 that Mounjaro (tirzepatide) met the main goal of a head-to-head heart trial by matching Trulicity (dulaglutide) at preventing cardiovascular death, heart attack or stroke in adults with type 2 diabetes and established atherosclerotic cardiovascular disease. The same trial found a 16% lower rate of death from any cause among people taking Mounjaro ^[1].

The study, called SURPASS-CVOT, enrolled 13,299 participants at 640 sites in 30 countries and ran about five years, with a median follow-up of four years ^[1]. Participants were randomly assigned to weekly injections of Mounjaro at the highest dose they could tolerate — 5 mg, 10 mg or 15 mg — or Trulicity 1.5 mg, which had shown a cardiovascular benefit in an earlier trial called REWIND ^[1].

On the primary endpoint, a composite of cardiovascular death, heart attack or stroke known as MACE-3, the rate was 8% lower with Mounjaro than with Trulicity (hazard ratio 0.92; 95.3% confidence interval 0.83 to 1.01; p = 0.086) ^[1]. The trial was built to test non-inferiority, defined in advance as the upper limit of the confidence interval falling below 1.05, and it met that bar ^[1]. Because the interval crosses 1.0, the result supports "at least as good as," not a proven advantage on that specific endpoint.

The rate of all-cause death was 16% lower with Mounjaro (hazard ratio 0.84; 95.0% confidence interval 0.75 to 0.94; p = 0.002) ^[1]. Lilly states that this endpoint, along with several other secondary measures, was not controlled for multiplicity-adjusted type 1 error, a statistical correction used when many comparisons are tested at once ^[1].

A pre-specified indirect comparison of matched patient-level data from REWIND and SURPASS-CVOT estimated that Mounjaro reduced MACE-3 by 28% (hazard ratio 0.72; 95.0% confidence interval 0.55 to 0.94) and all-cause death by 39% (hazard ratio 0.61; 95.0% confidence interval 0.45 to 0.82) compared with a "putative placebo" ^[1]. That analysis is an indirect comparison rather than a randomized placebo group.

Among other secondary findings, kidney function declined more slowly with Mounjaro in a high- or very-high-risk chronic kidney disease group, with a 3.54 mL/min/1.73 m2 difference in eGFR change at 36 months versus Trulicity (declines of 4.97 and 8.51 respectively; baseline mean 53.4) ^[1]. Average A1C fell 1.73% with Mounjaro versus 0.90% with Trulicity from a baseline of 8.39%, and body weight fell 12.06% (about 25.2 pounds) versus 4.95% (about 10.3 pounds) from a baseline of 92.6 kg, or 204.15 pounds ^[1]. Lilly also reported greater improvements in lipids and systolic blood pressure ^[1].

The most commonly reported side effects in both groups were gastrointestinal, generally mild to moderate and mostly resolving after dose increases were finished, Lilly said. Discontinuation because of adverse events was 13.3% with Mounjaro and 10.2% with Trulicity ^[1].

"The SURPASS-CVOT results show that Mounjaro preserved the cardioprotective benefit of Trulicity," said Kenneth Custer, Ph.D., executive vice president and president of Lilly Cardiometabolic Health ^[1].

Why it matters for patients

For people with type 2 diabetes and established heart disease, the results indicate that tirzepatide preserved the heart protection already shown by dulaglutide, a GLP-1 medicine, rather than clearly adding to it on the composite heart endpoint in this comparison ^[1]. The death, kidney, blood sugar and weight findings favored tirzepatide in this trial, but several of those measures were not adjusted for multiple comparisons, so the strength of the evidence differs by endpoint ^[1].

The results described here come from a trial in adults with type 2 diabetes and atherosclerotic cardiovascular disease, not from a trial in people using tirzepatide for obesity. Lilly says studies of tirzepatide in chronic kidney disease and in morbidity and mortality in obesity are ongoing, and those results have not been reported ^[1].

Mounjaro is approved in the U.S. for adults with type 2 diabetes to improve blood sugar, and the same molecule is approved as Zepbound for adults with obesity, for some adults who are overweight with at least one weight-related condition, and for moderate-to-severe obstructive sleep apnea with obesity ^[1].

What happens next

Lilly said detailed SURPASS-CVOT results will be presented at the European Association for the Study of Diabetes annual meeting in September 2025 and published in a peer-reviewed journal, and that it plans to submit the data to global regulatory authorities by the end of this year ^[1]. Whether the findings change any product label has not been disclosed.