Semaglutide is a drug to treat diabetes – marketed under the popular brands Ozempic or Wegovy – that had already demonstrated its ability to reduce the risk of cardiovascular events associated with obesity in diabetic patients, but a clinical trial has now proven that This medication may also reduce the incidence of death from cardiovascular causes – such as a heart attack or stroke – in overweight or obese adults who do not have diabetes.
The results of the ‘SELECT: Semaglutide and cardiovascular outcomes in overweight or obese patients who do not have diabetes’ trial – funded by Novo Nordisk (the pharmaceutical company that developed semaglutide) – were recently presented at the American Heart Association’s 2023 Scientific Sessions. and were published simultaneously in the New England Journal of Medicine, and show that semaglutide treatment reduced cardiovascular events by 20% in overweight or obese adults with cardiovascular disease who did not have diabetes.
“It is known that being overweight and obese increases the risk of suffering cardiovascular events. However, while reducing cardiovascular disease by treating high cholesterol, high blood pressure, and diabetes is standard practice, the concept of treating obesity to reduce cardiovascular complications has been hampered by a lack of evidence that “Pharmacological or lifestyle interventions for overweight or obesity improve cardiovascular outcomes,” explained Dr. Michael Lincoff, senior author of SELECT and vice chair of research in the Department of Cardiovascular Medicine at the Cleveland Clinic. “This marks the first pharmacological intervention for overweight or obesity that has been rigorously shown to reduce the risk of cardiovascular events,” he adds.
Weight loss and improvements in cardiovascular risk factors
Semaglutide is a GLP-1 receptor agonist medication that was initially approved by the US Food and Drug Administration (FDA) for adults with type 2 diabetes, and was subsequently also approved for chronic weight control in adults with obesity or overweight with al minus one weight-related comorbidity, in this case under the name Wegovy.
Its effects on weight loss are mainly related to appetite suppression, since “the drug helps the pancreas produce more insulin to reduce blood sugar and acts on the brain to induce a feeling of satiety. This causes you to eat less or in smaller portions,” they explain from the University of Utah Health. However, it has other actions that may reduce cardiovascular risk, such as improvements in glucose level, reduction in blood pressure, cholesterol levels and inflammation, and beneficial effects on the heart muscle and blood vessels.
“This study of semaglutide demonstrates the effectiveness of a new pathway to reduce the excess risk associated with obesity of major and life-threatening cardiovascular complications”
In the trial, patients with pre-existing cardiovascular disease treated with semaglutide lost an average of 9.4% of their body weight and experienced improvements in other cardiovascular disease risk factors. These people received weekly injections of semaglutide at a dose of 2.4 mg, and the treatment was shown to outperform placebo in reducing the risk of death from cardiovascular causes, non-fatal heart attacks, or non-fatal strokes over a median follow-up of 40 months.
The SELECT trial ran from October 2018 to June 2023 and included patients aged 45 years or older with pre-existing cardiovascular disease and a body mass index of 27 or higher, but no history of diabetes. Participants included 17,604 patients in 41 countries who had previously suffered a heart attack, stroke, or peripheral arterial disease. They were divided into two groups to receive weekly injections of 2.4 mg of semaglutide (8,803) or placebo (8,801). ). All of them also received standard treatment for cardiovascular diseases, such as cholesterol-modifying drugs, antiplatelet therapies, beta-blockers or other treatments.
During the trial, death from a cardiovascular event, nonfatal myocardial infarction (heart attack), or nonfatal stroke occurred in 6.5% of patients who were treated with semaglutide versus 8.0% of patients who received placebo: a 20% reduction in relative risk with semaglutide. Risk reductions were similar in men and women and across different ethnicities, patient ages, and baseline body weight levels.
There was a slightly higher rate of gallbladder disorders in the semaglutide group versus placebo (2.8% versus 2.3%, respectively), which had also occurred previously in other studies with GLP-1 agents. Importantly, semaglutide was not associated with increased risks of serious gastrointestinal disorders, pancreatitis, psychiatric disorders, or kidney injury.
“There is growing recognition that obesity and overweight are actually metabolic diseases, and yet effective therapies have been quite limited,” said Dr. Lincoff. “This study of semaglutide demonstrates the effectiveness of a new pathway to reduce the obesity-associated excess risk of major and life-threatening cardiovascular complications,” he concludes.
