Eli Lilly and Company (NYSE: LLY) today announced positive topline results from SURPASS-CVOT, a landmark Phase 3 cardiovascular outcomes trial directly comparing two incretin-based therapies in adults with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD).
The study evaluated Mounjaro® (tirzepatide)—a dual GIP/GLP-1 receptor agonist—against Trulicity® (dulaglutide), a GLP-1 receptor agonist previously shown to reduce cardiovascular risk in the REWIND trial. With over 13,000 participants across 30 countries followed for more than 4.5 years, SURPASS-CVOT is the largest and longest study of tirzepatide to date.
Primary Endpoint Achieved: Mounjaro demonstrated non-inferiority to Trulicity for MACE-3 (a composite of cardiovascular death, myocardial infarction, or stroke), with a hazard ratio of 0.92 (95.3% CI: 0.83 to 1.01), meeting the pre-specified margin for non-inferiority.
All-Cause Mortality: Mounjaro was associated with a 16% lower risk of death from any cause versus Trulicity (hazard ratio: 0.84; 95.0% CI: 0.75 to 0.94; p = 0.002).
Kidney Function: Among participants at high or very-high risk of chronic kidney disease, Mounjaro slowed eGFR decline by 3.54 mL/min/1.73 m² more than Trulicity at 36 months (p < 0.001).
Glycemic Control and Weight Loss: Mounjaro led to greater reductions in A1C (-1.73% vs. -0.90%) and body weight (-11.43 kg vs. -4.65 kg) at 36 months compared to Trulicity.
An indirect comparison using matched patient-level data from the REWIND and SURPASS-CVOT trials suggests Mounjaro may reduce:
MACE-3 by 28% (hazard ratio: 0.72; 95.0% CI: 0.55 to 0.94), and
All-cause mortality by 39% (hazard ratio: 0.61; 95.0% CI: 0.45 to 0.82) compared to a theoretical placebo.
“These results highlight Mounjaro’s potential to provide not only the cardiovascular benefit observed with Trulicity but also additional advantages in kidney protection and overall survival,” said Dr. Kenneth Custer, EVP and President, Lilly Cardiometabolic Health. “They reinforce the promise of Mounjaro as a leading treatment option for adults with type 2 diabetes and cardiovascular disease.”
Adverse events were consistent with the known safety profiles of both medications. Gastrointestinal issues were the most common side effects, generally mild to moderate in severity and mostly resolving after dose titration. Treatment discontinuation due to adverse events occurred in 13.3% of Mounjaro patients vs. 10.2% of those on Trulicity.
Lilly plans to present the full data set from SURPASS-CVOT at the European Association for the Study of Diabetes (EASD) Annual Meeting in September 2025, followed by submission to global regulatory authorities by the end of the year.