Wegovy Lowered Cardiovascular Risk in Real-World Study | ACC 2025

An analysis of real-world data has found that Wegovy (semaglutide) lowered the risk of major adverse cardiovascular events (MACE) in adults who are overweight or obese and have cardiovascular disease (CVD). The analysis was presented today at the American College of Cardiology Annual Scientific Session and Expo.

Compared with non-users, Wegovy 2.4 mg lowered the risk on a three-point composite endpoint of heart attack, stroke or all-cause death by 57%. For the composite endpoint that included five points (heart attack, stroke, hospitalization for heart failure, evidence of a coronary revascularization procedure, or all-cause death), Wegovy lowered the risk by 45%

Wegovy is Novo Nordisk’s semaglutide product to treat obesity. The company also markets the semaglutide products Ozempic and the oral Rybelsus, which both treat type 2 diabetes. In January 2025, the FDA approved Ozempic to reduce the risk of kidney disease worsening, kidney failure, and death due to cardiovascular disease in adults with type 2 diabetes and chronic kidney disease.

The SCORE study analyzed MACE outcomes among Wegovy users and non-users in real-world clinical practice. Investigators conducted a retrospective analysis of 27,963 patients from a database of medical and pharmacy claims linked to clinical and laboratory measurements, as well as a sample of patients who met similar inclusion criteria in the SELECT trial.

Related: Wegovy Cuts Risk of Serious Cardiovascular Events By 20%

Results from the SELECT trial showed that semaglutide reduced the risk of serious cardiovascular events by 20% in overweight and obese people with established cardiovascular disease. These data had been presented at the American Heart Association Scientific Sessions meeting in November 2023 and published in The New England Journal of Medicine the same month.

Stephen Gough

Although the SCORE study built on the results of the SELECT trial and showed use of Wegovy was associated with cardiovascular risk reduction in a real-world environment, the results of the two studies are not comparable, Stephen Gough, senior vice president and head of the chief medical office at Novo Nordisk, told Managed Healthcare Executive.

“SCORE is a retrospective, observational, real-world evidence study, and SELECT was a randomized phase 3 cardiovascular outcomes trial,” he said. “Real-world data analyses also have several limitations; results may reflect residual unmeasured confounding; while associations can be demonstrated, causal relationships cannot be definitively established.”

In the SCORE study, researchers used propensity score matching to adjust for differences between the treatment and the non-treatment group so that these are comparable. This is a commonly accepted methodology in observational research, and approximately 60 variables were being matched on, including age, sex, race/ethnicity, region, insurance type, initiation year, BMI, smoking history, comorbidities, procedures, medication use, and healthcare resource utilization.

For the SCORE trial, the MACE-3 composite endpoint (heart attack, stroke, or all-cause death) occurred in 42 of the 9,321 patients in the Wegovy group and 175 of the 18,642 patients in the non-user group.

The MACE-5 composite endpoint (heart attack, stroke, hospitalization for heart failure, evidence of a coronary revascularization procedure, or all-cause death) occurred in 88 of the 9,321 patients in the Wegovy group and 288 of 18,642 patients in the non-user group.

The 5-point MACE in SCORE and SELECT are different regarding hospitalization. The SCORE MACE-5 included hospitalization for heart failure, while SELECT MACE-5 included hospitalization for unstable angina.

A spokesperson told MHE they worked with key opinion leaders in the healthcare field to set up the SCORE study and took their considerations into the design. The 5-point MACE in SCORE reflects that guidance on what would be a relevant composite in real life, as unstable angina can be difficult to truly capture in real life.