Real-world SCORE study: semaglutide 2.4 mg cuts cardiovascular events by 45-57% in non-diabetic obese patients | Research

The takeaway

The SCORE real-world study shows semaglutide 2.4 mg reduced 3-point MACE by 57% (HR 0.43) and 5-point MACE by 45% (HR 0.55) in 9,321 overweight/obese patients with ASCVD but without diabetes.

57% MACE reduction
Real-world SCORE study confirms semaglutide 2.4 mg dramatically reduces cardiovascular events in non-diabetic obese patients with established heart disease

What the researchers found

rMACE-3 HR 0.43 (p<0.001); rMACE-5 HR 0.55 (p<0.001); MACE-3 HR 0.58 (p<0.01); MACE-5 HR 0.65 (p<0.001). Reduced all-cause mortality, CV mortality, HF hospitalization, incident T2DM, and kidney events. 9,321 vs 18,642 matched.

Why it matters

This is the first real-world confirmation of the SELECT trial findings, showing semaglutide 2.4 mg provides substantial cardiovascular protection in non-diabetic obese patients with existing heart disease.

How the study worked

Propensity-score matched cohort study from US database (2016-2023). 1:2 matching. 9,321 semaglutide 2.4 mg users. Mean follow-up 200 days. NCT06874751.

What this study cannot tell us

Observational—larger effect sizes than SELECT trial may reflect residual confounding. Short mean follow-up (200 days). US-only database. Interim analysis.

How to read the evidence

Large propensity-matched real-world study. Supports RCT findings but observational design means effect sizes should be interpreted cautiously.

When this study was published

Published in 2025; NCT06874751.

The bigger picture

The SELECT trial showed semaglutide reduces CV events in non-diabetic obesity. SCORE confirms this in real-world practice with even larger effect sizes, strongly supporting semaglutide as a cardiovascular drug for obese patients regardless of diabetes status.

Questions still open

Will longer follow-up maintain these large effect sizes?
Are the larger effects than SELECT due to real-world factors or confounding?
Should semaglutide 2.4 mg be standard care for obese ASCVD patients?

Common questions

Does semaglutide protect the heart in people without diabetes?

Yes. This large real-world study of 9,321 obese patients with existing heart disease—but without diabetes—found semaglutide 2.4 mg reduced major cardiovascular events by 45-57%, including heart attacks, strokes, and death. This confirms the SELECT clinical trial in real-world practice.

Is semaglutide 2.4 mg just for weight loss?

No. While it was initially approved for obesity, this study confirms it also substantially reduces cardiovascular events, death, heart failure hospitalizations, and kidney problems. It represents a shift from viewing semaglutide as a weight loss drug to recognizing it as a cardiovascular protective agent.

Read the original research

Lower risk of cardiovascular events in patients initiated on semaglutide 2.4 mg in the real-world: Results from the SCORE study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity in the Real World).

Diabetes, obesity & metabolism, 27(11), 6691-6704

View on PubMed ↗Publisher’s paper ↗

Citation

Smolderen, Kim G; Mena-Hurtado, Carlos; Zhao, Zhenxiang; Michalak, Wojciech; Faurby, Mads; Smolarz, B Gabriel; Kosiborod, Mikhail N; Song, Jinlin; Chen, Yan; Boland, Joanna; Nanna, Michael G. (2025). Lower risk of cardiovascular events in patients initiated on semaglutide 2.4 mg in the real-world: Results from the SCORE study (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity in the Real World).. Diabetes, obesity & metabolism, 27(11), 6691-6704. https://doi.org/10.1111/dom.70080