To the Editor, The SELECT trial marks a pivotal shift in cardiovascular prevention, demonstrating that semaglutide reduces major adverse cardiovascular events (MACE—defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) by 20% in individuals with obesity but without diabetes. 1 This landmark finding, involving 17, 604 participants across 41 countries, indicates that metabolic therapies can provide cardiovascular protection independent of glycemic control. 1 In SELECT, participants receiving semaglutide 2. 4 mg weekly achieved sustained 10. 2% weight loss over 4 years, with MACE occurring in 6. 5% versus 8. 0% with placebo (HR 0. 80, 95% CI 0. 72–0. 90, P < 0. 001). 1, 2 The absolute risk reduction of 1. 5% translates to preventing one cardiovascular event per 67 treated patients over 3. 3 years (Number Needed to Treat = 67), efficacy comparable to statin therapy in high-risk populations. 1 These benefits persisted despite 90% baseline statin use, challenging traditional approaches that separate metabolic, and cardiovascular disease management. However, accessibility disparities threaten to create a two-tiered prevention system. With monthly costs exceeding 1, 300 and limited insurance coverage, these medications remain inaccessible to high-risk populations who would benefit most. Real-world evidence reveals concerning gaps: Insurance coverage rates differ dramatically (78% high-income versus 14% low-income patients), leading to disparate treatment persistence (47% versus 35% at one year) and unequal cardiovascular protection outcomes. 3 The psychological dimensions of obesity treatment merit equal attention. Weight stigma affects 40%–50% of individuals with obesity, significantly undermining cardiovascular risk modification efforts. 4 While time-restricted eating interventions demonstrate metabolic benefits including blood pressure reduction in metabolic syndrome, 3 comprehensive approaches must address weight-related discrimination to optimize treatment adherence. Emerging clinical observations suggest that meaningful weight loss achieved with GLP-1 medications may reduce stigmatizing experiences, though dedicated research examining this relationship is needed. Integrating psychosocial support alongside pharmacotherapy remains essential for sustainable outcomes. 3 From a preventive medicine perspective, SELECT necessitates healthcare system reforms. Current fragmented approaches treating obesity, diabetes, and cardiovascular disease as separate entities must evolve toward integrated cardiometabolic care models. Public health professionals must advocate for policy changes ensuring equitable GLP-1 access, including Medicare coverage expansion, biosimilar development acceleration, and integration into preventive care guidelines. The convergence of metabolic and cardiovascular medicine offers transformative potential for primary prevention, but only if we address access barriers and provide comprehensive support addressing both physiological and psychological aspects of cardiometabolic disease. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
Ahmed A. Almohammadi (2026) studied this question.