Real-World Study: Semaglutide Lowers Cardiovascular Risk More Than Tirzepatide in Adults With Obesity and CVD

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Semaglutide 2.4 mg (Wegovy®) was associated with a 57% lower risk of heart attack, stroke, or death compared with tirzepatide in a real-world study of adults with obesity and established cardiovascular disease (CVD) but without diabetes, Novo Nordisk reported August 31, 2025, at the European Society of Cardiology (ESC) Congress in Madrid.

The STEER study analyzed data from the Komodo Research database, including US adults aged ≥45 years with overweight or obesity and CVD who initiated semaglutide or tirzepatide between May 2022 and January 2025. Each treatment cohort included 10 625 participants matched for baseline characteristics. The primary outcome was incidence of major adverse cardiovascular events (MACE), defined as heart attack, stroke, hospitalization for heart failure, coronary revascularization, or death.

In a sensitivity analysis of patients without treatment interruptions longer than 30 days, MACE occurred in 0.1% of semaglutide users compared with 0.4% of tirzepatide users, corresponding to a 57% relative risk reduction. In the full cohort, including those with treatment gaps, semaglutide was associated with a 29% lower risk of MACE compared with tirzepatide after an average follow-up of approximately eight months.

Investigators noted these findings complement results from the randomized SELECT trial, which showed a 20% reduction in cardiovascular events with semaglutide compared with placebo, and the SCORE real-world study, which also demonstrated lower cardiovascular event rates among semaglutide users.

Obesity is a major driver of cardiovascular morbidity and mortality, accounting for two-thirds of obesity-related deaths. While overall cardiovascular mortality has declined in recent decades, obesity-related cardiovascular deaths have increased.

The authors emphasized that real-world evidence can provide important confirmation of trial results, reflecting outcomes in broader patient populations outside of controlled research settings.

Reference: Novo Nordisk. Wegovy® cuts risk of heart attack, stroke, or death by 57% compared to tirzepatide in real-world study of people with obesity and cardiovascular disease. Press release. August 31, 2025. Accessed September 2, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=916422#