Semaglutide treatment linked to lower cardiovascular risk in real-world SCORE study

New real-world data (RWD) from Novo Nordisk show that the GLP-1 receptor agonist, semaglutide, significantly reduces the risk of major cardiovascular events in adults with obesity or overweight and established heart disease, reinforcing findings from the SELECT trial.

Novo Nordisk has presented new real-world evidence (RWE) at the recent American College of Cardiology Annual Scientific Session and Expo (ACC.25) showing that semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist,  is associated with a significantly reduced risk of cardiovascular (CV) events in adults who are overweight or have obesity and established cardiovascular disease (CVD). The SCORE (Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity in the Real World) analysis builds on the landmark SELECT trial, providing additional insight into the medication’s effectiveness in routine clinical settings.

SCORE is a large retrospective, observational cohort study including 27,963 US patients aged 45 and older with a body mass index (BMI) of 27 kg/m² or higher and established CVD, but no history of diabetes. Participants were divided into two groups: 9321 initiated semaglutide 2.4 mg, while 18,642 did not. The average follow-up period was 7.1 months for semaglutide users and 6.4 months for non-users.

Compared with non-users, adults treated with semaglutide 2.4 mg had a 57% lower risk of major adverse cardiovascular events (MACE), including heart attack, stroke, or death. These events occurred in fewer than 0.5% of users, versus nearly 1% of non-users. Additionally, semaglutide use was linked to a 45% reduction in a broader composite outcome that also included hospitalizations for heart failure and coronary revascularization. The analysis showed consistent benefit across individual endpoints, including lower risks of heart failure hospitalization, CV-related death, and all-cause mortality.

"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," said Jason Brett (Acting Principal Medical Head, Novo Nordisk). "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."

The study utilized a national US database linking administrative medical and pharmacy claims with clinical and laboratory data. To minimize bias, each semaglutide user was matched with two non-users using propensity scores based on demographics, obesity status, BMI, comorbidities, prior procedures, medication use, and healthcare resource utilization. Patient characteristics were well balanced between the matched groups.

While the findings are encouraging, the authors note several limitations typical of real-world observational studies. These include the potential for unmeasured confounding, the inability to confirm causality, and a relatively short follow-up period due to semaglutide 2.4 mg’s recent approval. The reliance on retrospective claims data may also exclude patients with inconsistent insurance coverage or those from underserved populations, limiting generalizability.