Semaglutide reduced cardiovascular events by 20% in adults with overweight or obesity and established cardiovascular disease who do not have diabetes, according to new research. Semaglutide is primarily prescribed for adults with type 2 diabetes but is also approved for chronic weight management in adults with obesity or overweight and have at least one other health issue. In the trial, patients treated with semaglutide lost an average of 9.4% of their body weight and experienced improvements in other risk factors for cardiovascular disease.
The findings of the ‘SELECT — Semaglutide and Cardiovascular Outcomes in Patients with Overweight or Obesity Who Do Not Have Diabetes’ trial were presented today at the American Heart Association’s Scientific Sessions 2023 and simultaneously published in the New England Journal of Medicine.
A Cleveland Clinic physician reported the findings of a multi-center, international clinical trial that showed semaglutide reduced cardiovascular events by 20% in adults with overweight or obesity and established cardiovascular disease who did not have diabetes.
Semaglutide is primarily used to treat type 2 diabetes in adults, but it is also approved for chronic weight management in adults who are obese or overweight and have at least one other health problem. Patients in the trial who were given semaglutide lost an average of 9.4% of their body weight and saw improvements in other risk factors for cardiovascular disease.
Overweight and obesity are known to increase a person’s risk of cardiovascular events. This marks the first pharmacologic intervention for overweight or obesity that’s been shown in a rigorous fashion to reduce the risk of cardiovascular events.
Michael Lincoff
The findings of the “SELECT — Semaglutide and Cardiovascular Outcomes in Patients with Overweight or Obesity Who Do Not Have Diabetes” trial were presented today at the American Heart Association’s Scientific Sessions 2023 and published simultaneously in the New England Journal of Medicine.
In the trial, for patients with preexisting cardiovascular disease and overweight or obese but without diabetes, weekly injections of semaglutide at a dose of 2.4 mg were superior to placebo in reducing the risk of death from cardiovascular causes, nonfatal heart attack, or nonfatal stroke over an average follow-up of 40 months.
“Overweight and obesity are known to increase a person’s risk of cardiovascular events.” However, while treating high cholesterol, high blood pressure, and diabetes to reduce cardiovascular disease is standard practice, the concept of treating obesity to reduce cardiovascular complications has been hampered by a lack of evidence that lifestyle or pharmacologic interventions for overweight or obesity improve cardiovascular outcomes,” said Michael Lincoff, M.D., SELECT’s lead author and vice chair for research in Cleveland Clinic’s Department of Cardiovascular Medicine. “This marks the first pharmacologic intervention for overweight or obesity that’s been shown in a rigorous fashion to reduce the risk of cardiovascular events.”
More than half the world population is projected to be overweight or obese by the year 2035. High body-mass index (BMI) is estimated to have accounted for 4 million deaths globally in 2015, more than two thirds of which were caused by cardiovascular diseases.
Semaglutide, a GLP-1 receptor agonist medication that was initially approved and is most commonly prescribed for adults with type 2 diabetes, was also approved by the FDA in 2021 for chronic weight management in adults who are obese or overweight and have at least one weight-related comorbidity. While semaglutide’s weight loss effects appear to be primarily due to appetite suppression, this drug has other actions that may reduce cardiovascular risk, such as improvements in glucose levels, decreases in blood pressure and cholesterol levels, reductions in inflammation, and beneficial effects on heart muscle and blood vessels.
In the SELECT trial, which ran from October 2018 through June 2023, researchers enrolled patients 45 years of age or older who had pre-existing cardiovascular disease and a body mass index of 27 or greater but no history of diabetes. Over 17,000 patients in 41 countries who had previously experienced a heart attack, stroke and/or had peripheral artery disease were enrolled and followed for an average of 40 months after being randomly assigned to receive once weekly injections of semaglutide 2.4 mg or placebo.
In addition to taking either semaglutide or placebo for the trial, all participants also received standard-of-care treatment for cardiovascular disease, such as cholesterol-modifying medications, antiplatelet therapies, beta blockers or other treatments.
Death from a cardiovascular event, nonfatal myocardial infarction (heart attack), or nonfatal stroke occurred during the trial in 6.5% of patients who were treated with semaglutide versus 8.0% of patients who received placebo — a 20% reduction in relative risk by semaglutide. Risk reductions were similar in men and women and across different ethnicities, patient ages, and baseline levels of body weight.
In this trial, there were no unexpected safety issues with semaglutide. Semaglutide was discontinued by 16.6% more patients than placebo (8.2%), primarily due to gastrointestinal symptoms such as nausea and diarrhea. These gastrointestinal symptoms are common with this class of medications, especially when the medication is first started or the dose is increased. The semaglutide group had a slightly higher rate of gallbladder disorders than the placebo group (2.8% vs. 2.3%, respectively), which has previously been reported in other studies with GLP-1 agents. Semaglutide was not linked to an increased risk of severe gastrointestinal disorders, pancreatitis, psychiatric disorders, or kidney injury.
“There’s growing recognition that obesity and overweight are really metabolic diseases, and yet, effective therapies have been quite limited,” Dr. Lincoff said. “This study of semaglutide demonstrates the effectiveness of a new pathway to reduce the excess risk associated with obesity of important and potentially deadly cardiovascular complications.”
One limitation of the trial is that it only included patients with pre-existing cardiovascular disease. The effects of semaglutide on primary prevention of cardiovascular events in people who are overweight or obese but have never had a heart attack were not studied.
