SELECT: Semaglutide vs. Placebo in Overweight or Obese Patients With Pre-Existing CVD, But Without Diabetes

In patients with pre-existing cardiovascular disease and who are overweight or obese, but who do not have diabetes, 2.4 mg of subcutaneous semaglutide taken once weekly was superior to placebo in reducing the risk of cardiovascular death, myocardial infarction (MI) or stroke, according to findings from the SELECT trial presented Nov. 11 at AHA 2023 and simultaneously published in the New England Journal of Medicine. Researchers noted the benefits of semaglutide were observed early and were concordant across subgroups and the trial’s cardiovascular endpoints.

SELECT randomized 17,604 patients (aged ≥45 years, BMI ≥27 kg/m2) from 41 countries who were overweight or obese with established cardiovascular disease and no history of diabetes to either once-weekly subcutaneous semaglutide (2.4 mg) or placebo. Of note, only adults with prior cardiovascular disease were included in the study and only 28% of participants were female. The primary endpoint was a composite of death from cardiovascular causes, nonfatal MI or nonfatal stroke.

According to the results, the primary cardiovascular endpoint event occurred in 569 of the 8,803 patients (6.5%) in the semaglutide group compared with 701 of the 8,801 patients (8.0%) in the placebo group over a mean follow-up of 39.8 months. Semaglutide was also associated with reductions in body weight and waist circumference compared with placebo, as well as reductions in cholesterol and tryglyceride levels and improvements in blood pressure. Researchers did note that a greater percentage of patients discontinued semaglutide vs. placebo, largely due to gastrointestinal symptoms (880 patients vs. 172 patients, respectively).

“It’s been estimated that within about 10 years, over half of the world’s population will have overweight or obesity,” said A. Michael Lincoff, MD, FACC. “Our findings expand the opportunity to treat patients who have overweight or obesity and existing heart disease without Type 1 or Type 2 diabetes, and we have a chance to significantly reduce their risk of a secondary cardiovascular event including death.”

A related editorial by Amit Khera, MD, MSc, FACC, and Tiffany M. Powell‑Wiley, MD, MPH, notes: “We are in a new era of treating obesity and cardiometabolic risk with a growing armamentarium of options ... However, we must continue to address the upstream underpinnings of obesity and the downstream effects on the communities that are the most vulnerable to the obesity epidemic and have the least access to these new treatment options.”

Clinical Topics: Acute Coronary Syndromes

Keywords: American Heart Association, AHA23, Acute Coronary Syndrome, Glucagon-Like Peptide-1 Receptor, Obesity

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