Lilly's Mounjaro Shows Promising Cardiovascular Benefits in Head-to-Head Trial with Trulicity

Eli Lilly has unveiled phase 3 results demonstrating that its dual-action GIP/GLP-1 therapy Mounjaro (tirzepatide) is comparable to the company's GLP-1 drug Trulicity in reducing cardiovascular risks among patients with Type 2 diabetes and heart disease. The findings from the Surpass-CVOT study mark a significant milestone in the evolving landscape of diabetes and cardiovascular treatments.

Surpass-CVOT Trial Results

The Surpass-CVOT study, involving 13,299 patients across 30 countries over a four-year period, achieved its primary objective by showing Mounjaro's noninferiority to Trulicity in reducing major adverse cardiovascular events (MACE-3) - cardiovascular death, heart attack, or stroke. Notably, Mounjaro patients demonstrated an 8% lower risk of cardiovascular events compared to those on Trulicity, with consistent results across all three MACE-3 components.

Additional benefits observed in the Mounjaro group included:

• Greater weight loss
• Reduced A1C levels, a key biomarker for Type 2 diabetes
• A 16% lower rate of all-cause mortality

Kenneth Custer, Ph.D., head of Lilly's cardiometabolic health unit, emphasized the significance of these findings, stating, "These findings strengthen the case for Mounjaro as a potential front-line treatment for people with type 2 diabetes and cardiovascular disease."

Comparative Analysis and Market Implications

While Lilly hailed the trial as "landmark," some analysts, including those from Citi, expressed a more measured response. The trial "misses the superiority scenario that many investors had hoped for," according to Citi analysts. However, they noted that even a non-inferiority outcome could be sufficient to influence prescribing habits, given Mounjaro's superior weight loss and tolerability profile compared to Novo Nordisk's semaglutide.

A pre-specified indirect comparison of matched patient-level data from the Rewind-CVOT study (Trulicity vs. placebo) and the Surpass-CVOT trial suggested that Mounjaro reduced the risk of MACE-3 by 28% and all-cause mortality by 39% compared to a putative placebo. This reduction meets the 20% threshold that cardiologists consider clinically meaningful.

Lilly plans to submit the results to regulatory authorities by the end of this year, with detailed data presentation scheduled for September at the European Association for the Study of Diabetes conference in Vienna.

Broader Context: GLP-1 Drugs and Cardiovascular Benefits

The cardiovascular benefits of GLP-1 drugs have been well-established in recent years. Novo Nordisk's Ozempic received FDA approval in 2020 to reduce cardiovascular risks in Type 2 diabetes patients, and in 2025, it gained an additional indication for reducing the risk of worsening kidney disease and cardiovascular death in patients with Type 2 diabetes and chronic kidney disease.

Lilly's portfolio expansion in this area includes:

• A 2024 approval for Zepbound as the first treatment for patients with obesity and sleep apnea
• Ongoing trials for dual-action drugs in heart failure, prediabetes, and metabolic dysfunction-associated steatohepatitis

As cardiovascular disease remains the leading cause of death among people with Type 2 diabetes, these developments represent crucial advancements in addressing this significant health concern.