Semaglutide Linked to Cardiovascular Gains, but Also Higher Health Spending

Prescribing semaglutide in routine clinical practice was associated with meaningful—but smaller than seen in clinical trials—improvements in cardiovascular risk factors, along with an unexpected rise in non-drug health care spending, according to a new study published in JAMA Network Open.1

Analyzing data from more than 23,500 adult patients across Yale New Haven Health System and Sentara Healthcare, researchers found that patients experienced an average 3.8% reduction in body weight and significant reductions in blood pressure (–1.5 mm Hg for diastolic; –1.1 for systolic), total cholesterol (–12.8 mg/dL), and hemoglobin A1c (HbA1C) at 13 to 24 months following their first semaglutide prescription. However, during the same time period, monthly health care expenditures rose by $80 per patient, not including the cost of semaglutide itself.

“These findings highlight a disconnect between clinical benefits and short-term cost savings, warranting caution when extrapolating trial-based projections to clinical settings,” the researchers said.

Monthly health care expenditures rose by $80 per patient. | Image credit: Nati – stock.adobe.com

Real-World Gains Smaller Than Clinical Trials

Patients without diabetes saw even greater benefits with semaglutide—a 5.1% weight reduction (95% CI, –5.5% to –4.7%) and a 1.9 mm Hg drop in systolic blood pressure (95% CI, −2.6 to −1.3 mm Hg), compared with reductions of 3.5% and 1.2 mm Hg, respectively, for those with diabetes. On the other hand, patients with diabetes experienced a larger drop in HbA1c (–0.3%) than those without (–0.1%).

These clinical improvements, although statistically significant, were more modest than those seen in clinical trials such as STEP 1 (NCT03548935), where weight reductions reached nearly 15% at 12 months among people with obesity and without diabetes.2

According to the authors, these findings show how differently semaglutide performs outside the ideal conditions of a randomized controlled trial, especially when considering real-world medication adherence.1 Of the total cohort, 82.7% of patients had at least 2 semaglutide prescriptions, with 57.6% maintaining active prescriptions during months 13 to 24. Based on prescribing patterns, the authors estimated that about 21% of patients had less than 3 months of treatment exposure, whereas less than 5% had 3 to 6 months of exposure and 7% had 6 to 12 months; the majority of the group continued with treatment past 12 months (67%).

Expenses Rise After Initiation

Despite the improvements in clinical markers, monthly health care spending rose significantly after semaglutide was prescribed. Excluding semaglutide costs, average monthly expenditures increased by $80 (95% CI, 68-92) in the second year of treatment, with $43 of that coming from inpatient costs. The rise was seen in both patients with and without diabetes, increasing by $67 and $81 per month, respectively. The largest spending increases were for circulatory ($15) and metabolic diagnoses ($21).

Clinically, the results support the need to incorporate anti-obesity medications like semaglutide into standard care, according to the authors, especially for individuals at elevated cardiovascular risk. At the same time, the rise in health care spending within 2 years of treatment highlights the ongoing tension between delivering clinical improvements and managing costs.

“Our results call into question whether glucagon-like peptide-1 receptor agonists will ‘pay for themselves’ through reduced expenditures of other kinds, at least in the short- to medium-term,” the researchers said.

References

1. Lu Y, Liu Y, Totojani T, et al. Changes in cardiovascular risk factors and health care expenditures among patients prescribed semaglutide. JAMA Netw Open. 2025;8(8):e2526013. doi:10.1001/jamanetworkopen.2025.26013
2. Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183