Mounjaro (tirzepatide), a GIP/GLP-1 dual receptor agonist, was evaluated for cardiovascular outcomes in patients with type 2 diabetes and established atherosclerotic cardiovascular disease in the SURPASS-CVOT trial (NCT04554433), the first head-to-head comparison of two incretin therapies. This phase 3, randomized, double-blind trial compared Mounjaro to Trulicity (dulaglutide), a GLP-1 receptor agonist with proven cardiovascular benefits in the REWIND study.
SURPASS-CVOT enrolled adults with type 2 diabetes and confirmed cardiovascular disease, randomizing them to receive either Mounjaro or Trulicity. The primary objective was non-inferiority in major adverse cardiovascular events (MACE-3: cardiovascular death, myocardial infarction, or stroke). Secondary outcomes included all-cause mortality, A1C reduction, weight loss, and changes in cardiovascular biomarkers (lipids, systolic blood pressure). Safety and tolerability were assessed, focusing on adverse events and discontinuation rates. Statistical analyses included time-to-first-event using Cox proportional hazard models and ANCOVA for baseline changes.
Mounjaro achieved non-inferiority versus Trulicity, reducing MACE-3 events by 8% (boundary for non-inferiority <1.05). It also demonstrated a 16% lower rate of all-cause mortality. Mounjaro led to significantly greater improvements in A1C, weight, lipids, and systolic blood pressure compared to Trulicity. Safety profiles were consistent with prior studies; gastrointestinal adverse events (nausea, diarrhea) were most common, mild-to-moderate, and typically resolved post-dose escalation. Discontinuation due to adverse events occurred in 13.3% of Mounjaro patients versus 10.3% for Trulicity. Serious side effects, including pancreatitis, hypoglycemia, and allergic reactions, were rare but noted, with warnings for thyroid cancer risk in patients with MTC or MEN 2 history.
Mounjaro demonstrated non-inferior cardiovascular protection compared to Trulicity in type 2 diabetes patients with cardiovascular disease, with superior glycemic and weight outcomes. Its safety profile aligns with established incretin therapies, supporting its use in this population. Detailed results will be presented at the European Association for the Study of Diabetes (EASD) 2025 meeting, with regulatory submissions planned by year-end. Further studies are needed to confirm long-term benefits and broader applicability.
