Novo Nordisk presented compelling real-world evidence at the European Society of Cardiology Congress 2025 showing that Wegovy (semaglutide 2.4 mg) demonstrated superior cardiovascular protection compared to tirzepatide in patients with obesity and established cardiovascular disease. The STEER study revealed a significant 57% greater risk reduction for major adverse cardiovascular events in patients who remained on continuous treatment.
Study Design and Population
The STEER study was a retrospective, observational real-world analysis that evaluated cardiovascular outcomes in 21,250 US adults with overweight or obesity and established cardiovascular disease without diabetes. Each treatment group comprised 10,625 participants matched using propensity score methodology to ensure comparable baseline characteristics.
The study utilized data from the US Komodo Research database spanning January 1, 2016, to January 31, 2025, focusing on patients aged 45 years and older who initiated treatment with either Wegovy or tirzepatide on or after May 13, 2022. Researchers employed rigorous matching protocols to compare patients with similar demographic and clinical profiles.
Primary Findings
In patients who maintained continuous treatment without gaps exceeding 30 days, Wegovy users experienced dramatically fewer cardiovascular events compared to tirzepatide users. Specifically, 15 patients (0.1%) in the Wegovy group experienced heart attack, stroke, cardiovascular-related death, or death from any cause, compared to 39 patients (0.4%) in the tirzepatide group over an average follow-up of 3.8 months and 4.3 months, respectively.
The broader analysis, including all treated patients regardless of treatment gaps, showed Wegovy maintained a significant 29% risk reduction for heart attack, stroke, and death from any cause compared to tirzepatide. Over an average follow-up of 8.3 months for Wegovy and 8.6 months for tirzepatide, 56 patients (0.5%) in the Wegovy group experienced these events compared to 83 patients (0.8%) in the tirzepatide group.
Clinical Significance and Expert Commentary
"Our landmark trial, SELECT, showed that Wegovy is associated with a significant 20% risk reduction of cardiovascular events, backed up with even greater risk reductions in the real-world studies SCORE and STEER," stated Ludovic Helfgott, executive vice president and head of Product & Portfolio Strategy at Novo Nordisk. "This data confirms that semaglutide stands apart as the only available GLP-1-based medication with proven cardiovascular benefits for people living with obesity and cardiovascular disease, without diabetes."
Anna Windle, Senior Vice President, Clinical Development, Medical and Regulatory Affairs at Novo Nordisk, emphasized the molecule-specific nature of these benefits: "In the STEER study, patients using Wegovy had greater cardiovascular improvements compared to tirzepatide, indicating that the same CV benefit cannot be generalized across other molecules in the GLP-1 or GIP/GLP-1 classes and may come specifically from the semaglutide molecule."
Supporting Evidence Base
The STEER findings complement results from the SELECT randomized controlled trial, which demonstrated Wegovy's superiority over placebo in reducing 3-point MACE (cardiovascular death, non-fatal heart attack, or non-fatal stroke) in patients with overweight or obesity and established cardiovascular disease without diabetes. The SELECT trial included participants aged 45 years and older with a body mass index of 27 kg/m² or greater.
Additionally, the SCORE real-world study previously analyzed MACE outcomes among Wegovy users and non-users in US clinical practice, providing further evidence of cardiovascular benefits in similar patient populations.
Disease Burden Context
The study addresses a critical medical need, as cardiovascular disease remains the leading cause of disability and death worldwide, claiming nearly 21 million lives annually. Obesity directly contributes to cardiovascular morbidity, mortality, and hospitalization. While overall cardiovascular mortality has decreased over the past two decades, obesity-related cardiovascular deaths have increased significantly, with two-thirds of obesity-related deaths linked to cardiovascular disease.
Study Limitations and Considerations
As with all real-world evidence studies, STEER has inherent limitations. While associations can be demonstrated, causal relationships cannot be definitively established. Results may reflect potential unmeasured confounding factors, and the relatively recent approval of both treatments limited follow-up duration. Administrative claims data may also be subject to coding inaccuracies.
The findings support growing evidence that cardiovascular benefits observed with Wegovy are specific to the semaglutide molecule and cannot be extended to other GLP-1 or GIP/GLP-1-based treatments, potentially influencing treatment selection for patients with obesity and cardiovascular disease.
