ACC 2025: Cardiovascular Benefits of Semaglutide 2.4 mg Highlighted in Real-World Study

People with atherosclerotic cardiovascular disease (ASCVD) and overweight or obesity but without diabetes who were initiated on semaglutide 2.4 mg in routine clinical care had a significantly lower risk of major adverse cardiovascular events (MACE) and all-cause mortality, according to a real-world study presented at the American College of Cardiology Annual Scientific Session and Expo (ACC.25) and simultaneously published in JACC.¹

The SCORE study (Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity in the Real World) analyzed data from a large claims and electronic medical records (EMR) database in the US, including patients aged 45 years or older with overweight or obesity and ASCVD but no diabetes. Using a nonparsimonious propensity score model, researchers matched 9321 patients who initiated semaglutide 2.4 mg with 18 642 nonusers in a 1:2 ratio to ensure well-balanced baseline characteristics. The analysis assessed the risk of both a revised MACE-3 composite (myocardial infarction, stroke, or all-cause death) and a revised MACE-5 composite (myocardial infarction, stroke, hospitalization for heart failure, coronary revascularization, or all-cause death).^1,2

Results showed that semaglutide 2.4 mg use was associated with a 57% lower risk of MACE-3 compared with non-users (HR 0.43, 95% CI 0.31-0.61; P < .001). The event rate for MACE-3 was 0.45% (42 of 9321) in the semaglutide group compared with 0.94% (175 of 18 642) in the non-user group. Semaglutide use was also associated with a 45% lower risk of MACE-5 (HR 0.55, 95% CI 0.43-0.70; P < .001), with events occurring in 0.94% (88 of 9321) of semaglutide users compared with 1.54% (288 of 18 642) of non-users. Additionally, semaglutide use was linked to significantly lower risks of hospitalization for heart failure, cardiovascular-related death, and all-cause death.^1,2

"Real-world analyses such as SCORE complement randomized controlled trials by offering healthcare professionals additional information about how therapies perform in routine clinical practice as they partner with patients on individualized treatment decisions," Jason Brett, MD, Acting Principal Medical Head at Novo Nordisk Inc., said in a company press release.² "Our mission is to drive change in how obesity is seen and treated, and the real-world evidence from SCORE provides actionable insights that can ultimately help improve patient care for people living with obesity at risk for CV events."

These findings reinforce the growing body of evidence supporting the use of glucagon-like peptide-1 (GLP-1) receptor agonists in cardiometabolic disease management. The results aligned with those of the SELECT clinical trial, which previously demonstrated cardiovascular benefits of semaglutide 2.4 mg in patients with overweight or obesity and established CVD.³ However, real-world data analyses such as SCORE have limitations, including potential residual confounding, limited follow-up duration due to the recent approval of semaglutide 2.4 mg, and the use of retrospective claims data, which may exclude certain populations. While associations can be demonstrated, causal relationships cannot be definitively established.¹

References:

1. Zhao, Z, Song, J, Faurby, M. et al. Lower risk of MACE and all-cause death in patients initiated on semaglutide 2.4 Mg in routine clinical care: Results from the SCORE study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity in the Real World). JACC. 2025;85:380. doi:10.1016/S0735-1097(25)00864-2

2. SCORE analysis of semaglutide 2.4 mg demonstrated reduction in cardiovascular events in a real-world setting. News release. Novo Nordisk. March 30, 2025. Accessed April 1, 2025. https://novonordisk.mediaroom.com/2025-03-30-SCORE-analysis-of-semaglutide-2-4-mg-demonstrated-reduction-in-cardiovascular-events-in-a-real-world-setting

3. Halsey G. Antiobesity medication semaglutide 2.4 mg reduced risk of MACE by 20%: Topline results from landmark SELECT trial. Patient Care Online. August 8, 2023. Accessed April 1, 2025. https://www.patientcareonline.com/view/antiobesity-medication-semaglutide-2-4-mg-reduced-risk-of-mace-by-20-topline-results-from-landmark-select-trial