The New England Journal of MedicineSemaglutide and Cardiovascular Outcomes in Obesity without Diabetes

The popular drug has the potential to be a therapeutic intervention for cardiovascular risk reduction.

A recent multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial has revealed that semaglutide, a glucagon-like peptide-1 receptor agonist, can reduce cardiovascular risk in overweight and obese patients without diabetes. This study provides significant insights into the potential of semaglutide as a therapeutic intervention for patients with preexisting cardiovascular disease.

Study Design

• The study enrolled patients aged 45 years or older who had preexisting cardiovascular disease and a body-mass index of 27 or greater but no history of diabetes.
• Patients were randomly assigned to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo.
• The primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis.

Key Findings

• A total of 17,604 patients were enrolled; 8,803 were assigned to receive semaglutide and 8,801 to receive placebo.
• A primary cardiovascular end-point event occurred in 6.5% of the patients in the semaglutide group and in 8.0% of the patients in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001).
• Adverse events leading to permanent discontinuation of the trial product occurred in 16.6% of the patients in the semaglutide group and 8.2% of the patients in the placebo group (P<0.001).

HCN Medical Memo
In this trial involving overweight or obese patients with preexisting cardiovascular disease but no diabetes, it was found that weekly doses of 2.4 mg of semaglutide were more effective than a placebo in reducing cardiovascular events. These events included death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke over an average follow-up period of 39.8 months. This suggests that semaglutide could be a promising treatment for reducing cardiovascular risk in this patient population.

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