SCORE analysis of Wegovy® (semaglutide injection) 2.4 mg demonstrates reduction of cardiovascular events in adults living with obesity and known heart disease

Novo Nordisk presented new data from the retrospective, observational SCORE study that assessed treatment with Wegovy® (semaglutide injection) 2.4 mg and the risk of major adverse cardiovascular events (MACE) in adults living with overweight or obesity and established cardiovascular disease (CVD).

The real-world analysis was presented at the American College of Cardiology 74th Annual Scientific Session and Expo (ACC.25).

Compared with non-users, semaglutide 2.4 mg use was associated with a significantly lower risk of revised MACE-3 composite endpoint (heart attack, stroke, or all-cause death) by 57 per cent (HR: 0.43; 95 per cent CI: 0.31-0.61; p < 0.001).1 Revised MACE-3 occurred in 42 (0.45 per cent) of the 9,321 patients in the semaglutide 2.4 mg group and 175 (0.94 per cent) of the 18,642 patients in the non-user group. The mean follow-up duration was 7.1 months for semaglutide users and 6.4 months for non-users.

Additionally, compared with non-users, semaglutide 2.4 mg use was associated with a significantly lower risk of revised MACE-5 composite endpoint (heart attack, stroke, hospitalisation for heart failure (HF), evidence of a coronary revascularisation procedure, or all-cause death) by 45 per cent (HR: 0.55; 95 per cent CI: 0.43-0.70; p < 0.001). Revised MACE-5 occurred in 88 (0.94 per cent) of the 9,321 patients in the semaglutide 2.4 mg group and 288 (1.54 per cent) of 18,642 patients in the non-user group.

SCORE results were consistent across a variety of CV endpoints, including death. Compared with non-users, semaglutide 2.4 mg use was also associated with significantly lower risk of incidence of HF HR 0.46 (95 per cent CI 0.29-0.73) p<0.01, CV-related death HR 0.27 (95 per cent CI 0.11-0.63) p<0.001, and all-cause death HR 0.14 (95 per cent CI 0.06-0.30), p<0.001.

Real-world study data can provide valuable insights into how treatments work outside of controlled settings. However, such studies often also have significant limitations which mean caution should be applied when trying to interpret the results. As in all observational studies, results may reflect residual unmeasured confounding; while associations can be demonstrated, causal relationships cannot be definitively established.

The data in SCORE were collected for administrative purposes, not clinical research, and there may be misclassification. The relatively recent approval of semaglutide 2.4 mg limited follow-up duration, restricting the assessment of long-term benefits. Additionally, use of retrospective claims data may exclude patients with intermittent coverage or underserved populations, potentially further limiting both interpretability and generalisability. Also , safety data or adverse events were not specifically sought as part of the SCORE study.