Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1s) are effective for weight loss. Moreover, the SELECT trial showed that semaglutide reduced cardiovascular disease (CVD) events in adults without diabetes and with established CVD. However, it is unknown whether GLP-1s are preferentially prescribed to those with higher CVD risk in real-world practice. We aimed to describe GLP-1 use by CVD status and by CVD risk, estimated using the American Heart Association’s PREVENT equation, among adults without diabetes. Methods: We analyzed electronic health record data from Geisinger, a large regional health system in Pennsylvania, USA, and identified GLP-1 users and non-users between June 2021 and February 2025. We included adults aged 30-79 years (the PREVENT equation age range) without diabetes and body mass index (BMI) ≥27 kg/m² at GLP-1 initiation or a randomly selected clinic visit (for non-users). Distributions of BMI and 10-year total CVD (atherosclerotic CVD and heart failure) risk from the PREVENT primary equation were compared by GLP-1 use. We employed multivariable logistic regression to assess associations between CVD risk categories (low <5%, borderline 5-7. 4%, intermediate 7. 5-19. 9%, high ≥20%, prevalent CVD, and unknown risk) and GLP-1 use, adjusting for age, sex, BMI, and use of antihypertensive agent and statin. Results: Of 204, 786 adults without diabetes and with BMI ≥27 kg/m², there were 16, 248 (7. 9%) GLP-1 users, and 15% had prevalent CVD. Compared with non-users, GLP-1 users were younger (mean 52 vs. 57 years), more often female (71 vs. 55%), and had higher BMI (mean 39 vs. 34 kg/m², p<0. 001; Figure 1). Among people without CVD, GLP-1 users had lower 10-year PREVENT total CVD risk than non-users (mean 5. 3 vs. 7. 7%, p <0. 001; Figure 2). Higher CVD risk was associated with lower GLP-1 use (low risk: 11. 4%; borderline: 8. 6%; intermediate: 5. 6%; high: 3. 2%; prevalent CVD: 7. 1%), with adjusted odds ratios of 0. 41 (95% CI, 0. 36-0. 48) and 0. 65 (0. 61-0. 69) for high risk and prevalent CVD, respectively, compared with low risk (Table 1). Conclusions: Among patients without diabetes, GLP-1s were more often prescribed to those at lower CVD risk in clinical practice, despite evidence of cardiovascular benefits primarily in patients with established CVD. Weight loss may have been prioritized in treatment decisions. This risk–treatment paradox underscores the need for risk-based prescribing to better reach patients most likely to benefit.
Yang et al. (Tue,) studied this question.