NEJM Original Article

The New England Journal of Medicine, December 14, 2023

A total of 17,604 patients were enrolled in a multicenter, double-blind, randomized placebo-controlled, event-driven superiority trial of individuals 45 years of age or older who had preexisting cardiovascular disease and BMI of 27 or greater, but no history of diabetes.

What’s Interesting about this article?

  • In this patient group, weekly subcutaneous semaglutide at a dose of 2.4 mg was superior to placebo in reducing the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke at mean follow-up pf 39.8 months.
  • The study was funded by Novo Nordisk, the drug manufacturer and conducted at the Cleveland Clinic in Cleveland Ohio.
  • Semaglutide improved cardiovascular outcomes in patients that had not responded to lifestyle interventions or other drug interventions.

JournalDoc Comments:

  • This is a very large study group at a top tier U.S. major medical center.
  • An accompanying editorial by Amit Khera, MD and Tiffany Powell-Wiley, MD, MPH, points out that the beneficial cardiac effects were obtained in addition to a 9.4% weight loss. This is a major finding for the over 20 million patients in the U.S. with coronary artery disease who are also obese.
  • The editorial also considers that the current pricing of semaglutide makes this drug inaccessible for many, which may limit its overall impact on public health.


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