Allocation of Semaglutide According to Coronary Artery Calcium and BMI: Applying the SELECT Trial to MESA

Background: Implementation of semaglutide weight loss therapy has been challenging due to drug supply and cost, underscoring a need to identify those who derive the greatest absolute benefit. Objectives: Allocation of semaglutide was modeled according to coronary artery calcium (CAC) among individuals without diabetes or established atherosclerotic cardiovascular disease (CVD). Methods: In this analysis, 3,129 participants in the MESA (Multi-Ethnic Study of Atherosclerosis) without diabetes or clinical CVD met body mass index criteria for semaglutide and underwent CAC scoring on noncontrast cardiac computed tomography. Cox proportional hazards regression assessed the association of CAC with major adverse cardiovascular events (MACE), heart failure (HF), chronic kidney disease (CKD), and all-cause mortality. Risk reduction estimates from the SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity) trial (median follow-up: 3.3 years) were applied to observed incidence rates for semaglutide 5-year number-needed-to-treat calculations. Results: Mean age was 61.2 years, 54% were female, 62% were non-White, mean body mass index was 31.8 kg/m², and 49% had CAC. Compared with CAC = 0, CAC ≥300 conferred a 2.2-fold higher risk for MACE (HR: 2.16 [95% CI: 1.57-2.99]; P < 0.001). Higher risks for HF (HR: 2.80 [95% CI: 1.81-4.35]; P < 0.001), CKD (HR: 1.59 [95% CI: 1.15-2.22]; P = 0.006), and all-cause mortality (HR: 1.35 [95% CI: 1.08-1.69]; P = 0.009) comparing CAC ≥300 vs CAC = 0 were also observed. There were large 5-year number-needed-to-treat differences between CAC = 0 and CAC ≥300 for MACE (653 vs 79), HF (1,094 vs 144), CKD (1,044 vs 144), and all-cause mortality (408 vs 98). Conclusions: Measurement of CAC may enhance value of care with weight loss dose semaglutide in those without diabetes or clinical CVD, improving allocation of a limited health care resource.