Tilpotide/Mufenta and SURPASS-CVOT backline results

On July 31, 2025, Eli Lilly announced topline data from the SURPASS-CVOT trial, which compared tirzepatide-Mounjaro with dulaglutide in adults with type 2 diabetes and diagnosed atherosclerotic cardiovascular disease (ASCVD).

According to the data, tilpotide met the primary non-inferiority endpoint of 3-point major adverse cardiovascular events (MACE) (hazard ratio [HR], 0.92; 95.3% CI, 0.83 to 1.01), while also showing additional benefit in A1C, weight loss, renal protection and a 16% reduction in all-cause mortality (HR, 0.84; 95.0% CI, 0.75 to 0.94). In the latest issue, the latest results of the SURPAS-CVOT trial were announced. Both drugs, owned by Eli Lilly, are in the incretin class, but tilpotide is a dual GIP/GLP-1 receptor agonist, while dulaglutide is a GLP-1 RA.

The trial included more than 13,000 adults with type 2 diabetes who either had cardiovascular disease or were at high risk. During a median follow-up of 4.5 years, the primary endpoint (composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) was reduced by 8% in the tilpotide group compared with dulaglutide. However, the results did not reach statistical superiority because the confidence intervals were uniform across crossovers.

The study also highlighted that tilpotide significantly improved A1c (-1.73% vs. -0.9%) and weight loss (12% vs. 4.95%). Additional prespecified analyzes comparing data from the placebo-controlled REWIND trial showed that tilpotide could provide up to a 28% reduction in MACE and a 39% risk reduction in mortality compared with theoretical placebo, findings that hint at broader cardiometabolic benefits.

Before concluding, the moderator speculated on subgroup analyzes that may be of interest for the trial, including heart failure and renal outcomes, and briefly discussed Eli Lilly's intention to submit a regulatory application for the cardiovascular indication by the end of 2025.

Reference materials:https://www.hcplive.com/view/diabetes-dialogue-tirzepatide-and-surpass-cvot-topline-results