Semaglutide cuts risk of heart attack, stroke or death by 57% vs tirzepatide

Outcomes form the STEER real-world study have revealed that semaglutide 2.4 mg had 57% greater risk reduction for heart attack, stroke and cardiovascular-related death or death from any cause, in people with overweight or obesity and CVD, who did not have any gaps in their treatment lasting more than 30 days, compared with tirzepatide. The findings were presented at the European Society of Cardiology (ESC) Congress 2025 in Madrid, Spain.

There were 15 (0.1%) of these cardiovascular events recorded with semaglutide and 39 events (0.4%) were recorded with tirzepatide. The average follow-up duration was 3.8 months for the semaglutide group and 4.3 months for the tirzepatide group.

In all treated people, regardless of any gaps in their treatment, semaglutide showed a significant 29% risk reduction for heart attack, stroke and death from any cause compared with tirzepatide (over an average follow-up of 8.3 months for semaglutide and 8.6 months for tirzepatide).

“Our landmark trial, SELECT, showed that Wegovy (semaglutide) 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. The results are clear - STEER demonstrates that Wegovy cuts the risk of heart attack, stroke or death by 57% compared to tirzepatide,” said 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.”

Additionally, in all treated people, regardless of any gaps in their treatment, people treated with semaglutide experienced fewer events of heart attack, stroke and cardiovascular-related death than people treated with tirzepatide.

STEER was a retrospective, observational real-world study, evaluating the efficacy of semaglutide 2.4 mg versus tirzepatide for the prevention of MACE in US adults with overweight or obesity and established CVD with no prior history of diabetes, with a primary outcome measure of revised 5-point MACE (heart attack, stroke, hospitalisation for heart failure, coronary revascularisation, and death from any cause) and revised 3-point MACE (heart attack, stroke and death from any cause). Non-revised 5-point and 3-point MACE was also studied, which included cardiovascular-related death rather than death from any cause.

The study included people from the US Komodo Research database (1 January 2016 to 31 January 2025) aged ≥45 years and started treatment with semaglutide or tirzepatide on or after 13 May 2022. Each treatment group comprised 10,625 people. To ensure both groups were comparable, researchers used propensity score matching to compare semaglutide users and tirzepatide users with similar characteristics. After matching, characteristics were well-balanced between the treatment groups.

The main analysis included all people who started treatment, regardless of any gaps in their therapy, while a sensitivity analysis evaluated outcomes only in people who did not have any gaps in their treatment lasting more than 30 consecutive days.