SELECT Trial: Semaglutide Cuts Major CVD Risk by 20% in Overweight/Obese Adults Without Diabetes

The results of the SELECT trial show that people who are overweight or obese but do not have diabetes taking semaglutide for more than 3 years had a 20% risk reduction of heart attack, stroke, or death due to cardiovascular disease (CVD) and lost over 9% of body weight. The results were presented in a late-breaking science presentation today at the American Heart Association’s Scientific Sessions 2023, taking place Nov. 11-13, in Philadelphia, PA, and simultaneously published today in The New England Journal of Medicine.

Worldwide rates of obesity have jumped appreciably since the 1980s, and the 2023 World Obesity Atlas estimates that over half of the world’s population will be overweight or obese by 2035. Such an estimation is concerning given the link between obesity and developing CVD and premature cardiovascular death, highlighting the need for effective treatments.

Viable Treatment for a Worldwide Problem

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist, a class of therapies which work by simulating the functions of the body’s natural incretin hormones, which aids in reducing blood sugar levels following a meal. The therapy was first approved by the FDA for treatment of Type 2 diabetes and, in 2021, it was approved for chronic weight management in adults with obesity.

In SELECT, a large, international clinical trial, researchers enrolled over 17,500 people (72% male) across 41 countries beginning in 2018. The population of interest were all 45 years of age or older, and 70% were obese, with a BMI of 30 or higher. All participants had a history of CVD, with a prior history of myocardial infarction, stroke, or peripheral artery disease, and none of the study subjects had Type 1 or 2 diabetes at the start of the study; however, between 5.7% to 6.4% met the criteria for prediabetes.

Study participants were randomly assigned to 2.4 milligrams of semaglutide (injected via a “pen”) or a placebo once a week, with a mean follow-up of 40 months. The trial participants also received standard of care treatment for CVD, which included cholesterol controlling medications and beta blockers.

The Findings Are “Very Encouraging”

Following analysis, the findings demonstrated a 20% reduction in the in the heart attacks, strokes, or death in patients taking semaglutide versus the placebo arm. Moreover, the semaglutide group on average reduced their body weight by 9.4% compared to only 0.9% in the placebo group. There were also no new safety concerns found in the SELECT trial, and the number of serious adverse events was lower in the semaglutide group.

“This news is very encouraging for people with overweight or obesity because no treatment specifically directed at the management of obesity and overweight in people without Type 1 or Type 2 diabetes has been tested in a randomized trial and been shown to influence cardiovascular outcomes,” said lead study author A. Michael Lincoff, M.D., vice chairman for research of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine and an interventional cardiologist in the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at the Cleveland Clinic via a press release.

“It’s been estimated that within about ten years, over half of the world’s population will have overweight or obesity,” said Dr. Lincoff. “And while GLP-1 medications are frequently prescribed for patients with vascular disease and Type 2 diabetes, there is a significant number of people who do not have Type 1 or Type 2 diabetes but do have vascular disease and overweight or obesity for whom these medications are often not available due to access to care issues, insurance coverage or other factors. This population may now potentially benefit from semaglutide, and importantly, our results indicate the magnitude of cardiovascular risk reduction with semaglutide among people without Type 1 or Type 2 diabetes is the same as what we have seen in people with Type 2 diabetes. 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.”