Semaglutide 2.4 mg reduces burden of total cardiovascular events in people with established cardiovascular disease and overweight or obesity
A new sub-analysis of the SELECT trial data shows semaglutide 2.4 mg substantially reduces the burden of total cardiovascular events in people with established CVD and overweight or obesity without diabetes, compared to placebo.1 Presented at the American College of Cardiology’s 74th Annual Scientific Session & Expo (ACC 2025) (29-31 March 2025, Chicago, Illinois), these results add to the body of evidence from the SELECT cardiovascular outcomes trial, providing data on the benefits of semaglutide 2.4 mg beyond the first cardiovascular event.1
These findings are important as primary analyses of large cardiovascular outcome trials typically assess only the first event, whereas people with obesity who are at high cardiovascular risk may experience multiple events over time, therefore the health burden of living with the disease and being at risk of injury and dying prematurely is not fully captured by these analyses. 1,5
In this prespecified secondary analysis of the SELECT trial, semaglutide 2.4 mg reduced the risk of first occurrence of a major adverse cardiovascular event (MACE) by 20% (HR 0.80; 95% CI 0.73–0.87; P<0.001) compared to placebo and reduced total events (first and subsequent) by 22% (MR 0.78; 95% CI 0.70–0.86; P<0.001). 1 Semaglutide 2.4 mg also reduced total heart attacks by 31% (MR 0.69; 95% CI 0.58–0.82; P<0.001) and total coronary revascularisations by 26% (MR 0.74; 95% CI 0.65–0.84; P<0.001) compared to placebo, driving the overall reduction in total cardiovascular events.1
Among 17,604 participants followed for a mean of 39.8 months, 3,031 cardiovascular events occurred, with 1,947 (64%) as first events and 1,084 (36%) as subsequent events.1 Coronary revascularisation represented 27.2% of first events and 72.9% of subsequent events, while heart attacks made up 26.2% of first events and 10.3% of subsequent events.1
Overall, this new SELECT sub-analysis shows that semaglutide 2.4 mg substantially reduces the first, subsequent, and total cardiovascular events in people with established CVD and overweight or obesity without diabetes,1 reinforcing its potential to reduce cardiovascular risk in addition to the health benefits already established with semaglutide 2.4 mg.4,6-16
About obesity and cardiovascular disease
Obesity is a chronic disease that directly leads to cardiovascular morbidity, mortality and hospitalisation,17,18 with two in three obesity-related deaths linked to CVD.2,3 Obesity is also associated with risk factors such as high blood pressure, chronic kidney disease and inflammation.19 Timely intervention for people with CVD and overweight or obesity is crucial to reduce residual risk for MACE, including
heart attack or stroke.5 Despite therapeutic advances, there remains a significant unmet need for effective treatment options that can address the diseases associated with obesity.20
About the SELECT trial
SELECT was an international randomised, double-blind, parallel-group, placebo-controlled trial designed to evaluate the efficacy of semaglutide 2.4 mg versus placebo as an adjunct to standard of care for prevention of MACE in people with established CVD with overweight or obesity with no prior history of diabetes.9 People included in the trial were aged ≥45 years with a BMI ≥27 kg/m2 and were followed for a period of up to five years.9
The primary objective of the SELECT trial was to demonstrate the superiority of semaglutide 2.4 mg compared to placebo with respect to reducing the incidence of three-point MACE consisting of cardiovascular death, non-fatal heart attack (myocardial infarction) or non-fatal stroke.4 Key secondary objectives were to compare the effects of semaglutide 2.4 mg to placebo with regards to mortality, heart failure, cardiovascular risk factors including glucose metabolism, body weight and kidney function.4
The trial, initiated in 2018, enrolled 17,604 adults and was conducted in 41 countries at more than 800 investigator sites.
The SELECT primary data was first presented at the American Heart Association Congress in November 2023 and simultaneously published in the New England Journal of Medicine.4 The trial has up to now provided various data sets and sub-analyses, presented at scientific congresses across the spectrum of cardiovascular, kidney and metabolic diseases, as well as publications in well-known scientific journals.4,10-16
