Cardiovascular Outcomes in Low-Risk Non-Diabetic Patients Treated with Semaglutide

Semaglutide use has been shown to reduce cardiovascular events in overweight/obese patients with diabetes and preexisting cardiovascular disease. However, data are limited on the benefit of semaglutide in populations without diabetes and with a low level of preexisting cardiovascular disease. Using claims data from Optum’s de-identified Market Clarity Data, we conducted an observational cohort study to evaluate mortality and cardiovascular outcomes associated with use of semaglutide in overweight/obese patients without diabetes or prior cardiovascular disease (myocardial infarction, stroke, or symptomatic peripheral arterial disease). A total of 38,234 patients who initiated semaglutide between April 2021 and March 2023 were propensity score matched 1:1 to control patients meeting study inclusion and exclusion criteria. Semaglutide patients were treated for a mean (SD) duration of 355 ± 261 days. Semaglutide patients and controls were followed for a mean (SD) duration of 20.2 ± 6.7 and 20.0 ± 6.5 months, respectively. In a time to first event analysis, a composite cardiovascular endpoint (all-cause mortality, nonfatal myocardial infarction or nonfatal ischemic stroke) occurred in 448 (1.2%) semaglutide patients and 645 (1.7%) control patients (HR = 0.73; 95% CI: [0.65, 0.82]; P<0.001). Individual components of the composite endpoint were also significantly lower in the semaglutide group. These findings provide evidence of potential benefit of semaglutide for cardiovascular risk reduction in a population with minimal baseline cardiometabolic complications. Given the population health implications, clinical trials of semaglutide in low risk populations are indicated.