Changes in Cardiovascular Risk Factors and Health Care Expenditures Among Patients Prescribed Semaglutide

Importance Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated substantial weight reduction and cardiovascular benefits in clinical trials. However, its association with clinical outcomes and health care expenditures remains underexplored. Objective To evaluate changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide across multicenter cohorts. Design, Setting, and Participants This retrospective cohort study included 23 522 adults (≥18 years) who received an initial semaglutide prescription between January 1, 2018, and January 1, 2025, at Sentara Healthcare and between January 1, 2018, and May 1, 2025, at Yale New Haven Health System. Exposure The first prescription of semaglutide identified at the ingredient level, stratified by type 2 diabetes status. Main Outcomes and Measures Primary outcomes included changes in weight (% baseline), blood pressure (BP), total cholesterol, and hemoglobin A 1c. Secondary outcomes assessed health care expenditures using Medicare-based cost estimates. A staggered difference-in-differences design compared outcomes of patients after the first semaglutide prescription with those of patients who had not yet received their prescription during the same period. Results The study cohort included 23 522 patients (mean SD age at initiation of semaglutide, 56. 2 12. 9 years; 66. 7% female; 68. 6% with diabetes). In the overall cohort, initiation of semaglutide was significantly associated with a −3. 8% (95% CI, −3. 9% to −3. 7%) reduction in weight at 13 to 24 months, with a −5. 1% (95% CI, −5. 5% to −4. 7%) reduction in weight among patients without diabetes. Significant reductions in diastolic BP (−1. 5 mm Hg; 95% CI, −1. 7 to −1. 4 mm Hg), systolic BP (−1. 1 mm Hg; 95% CI, −1. 4 to −0. 8 mm Hg), and total cholesterol (−12. 8 mg/dL; 95% CI, −14. 3 to −11. 4 mg/dL) were also observed. Hemoglobin A 1c reductions were greater among patients with diabetes (−0. 3%; 95% CI, −0. 3% to −0. 2%) compared with patients without diabetes (−0. 1%; 95% CI, −0. 2% to −0. 01%). Imputed health care expenditures, excluding the cost of semaglutide, increased by 80 per month (95% CI, 68-92 per month) during the 13- to 24-month period, which was associated with inpatient stays shifting to more expensive circulatory and metabolic diagnoses. Conclusions and Relevance In this cohort study of adults prescribed semaglutide, initiation was associated with reductions in weight and cardiovascular risk factors but increases in health care expenditures, excluding semaglutide costs. These findings suggest potential clinical benefits in routine practice, while highlighting the need to evaluate the long-term impact of semaglutide on economic outcomes.