On July 31, 2025, Eli Lilly and Company announced topline data from the SURPASS‑CVOT trial comparing tirzepatide (Mounjaro) to dulaglutide (Trulicity) in adults with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD). According to the data, tirzepatide met the primary non‑inferiority endpoint for 3-point major adverse cardiovascular events (MACE) (hazard ratio [HR], 0.92; 95.3% CI, 0.83 to 1.01), while also showing additional benefits in A1C, weight reduction, renal preservation, and a 16% reduction in all‑cause mortality (HR, 0.84; 95.0% CI, 0.75 to 0.94). In the latest episode of Diabetes Dialogue: Technology, Therapeutics, and Real-World Perspectives, Diana Isaacs, PharmD, an endocrine clinical pharmacist, director of Education and Training in Diabetes Technology, and co-director of Endocrine Disorders in Pregnancy at the Cleveland Clinic, and Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center, unpacked the top-line results of the SURPASS-CVOT trial. Eli Lilly and Company owns both drugs, which belong to the incretin class, but tirzepatide is a dual GIP/GLP-1 receptor agonist, while dulaglutide is a GLP-1 RA. The trial included over 13,000 adults with type 2 diabetes and either established cardiovascular disease or at high risk. During a median follow-up of 4.5 years, the primary endpoint, which was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, was reduced by 8% in the tirzepatide group relative to dulaglutide. However, the result did not reach statistical superiority due to the confidence interval crossing unity. Isaacs and Bellini also highlighted significantly greater A1c (-1.73% vs -0.9%) and weight loss (12% vs 4.95%) with tirzepatide. Additional prespecified analyses comparing data with the placebo-controlled REWIND trial suggest tirzepatide could offer up to 28% MACE and 39% mortality risk reduction compared to theoretical placebo—findings that hint at broader cardiometabolic benefit. Before concluding, hosts speculated about the potential subgroup analyses of interest for the trial, including heart failure and renal outcomes, as well as a brief discussion around Eli Lilly and Company’s intent to submit a regulatory application for a cardiovascular indication before the close of 2025. Relevant disclosures for Isaacs include Eli Lilly and Company, Novo Nordisk, Sanofi, Abbott Diabetes Care, Dexcom, Medtronic, and others. Relevant disclosures for Bellini include Abbott Diabetes Care, MannKind, Provention Bio, and others. References: Eli Lilly and Company. Lilly's Mounjaro (tirzepatide), a GIP/GLP-1 dual agonist, demonstrated cardiovascular protection in landmark head-to-head trial, reinforcing its benefit in patients with type 2 diabetes and heart disease. July 31, 2025. Accessed July 31, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated
