Washington, September 24 — A new analysis of clinical trial data suggests that the reduced risk of heart disease seen in people who are overweight or have obesity and take semaglutide may not be due solely to weight loss. The findings, announced on September 24, indicate that semaglutide should be considered a cardiovascular disease reduction drug and not just a weight loss drug.
Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist originally approved by the US Food and Drug Administration in 2017 under the brand name Ozempic for the treatment of type 2 diabetes. In 2021, the FDA approved semaglutide under the brand name Wegovy for chronic weight management in adults with obesity or overweight with at least one weight-related condition.
The drug works by mimicking the GLP-1 hormone, which increases insulin secretion, slows gastric emptying, and reduces appetite.
What the SELECT trial found
The SELECT cardiovascular outcomes trial, which enrolled approximately 17,600 adults with overweight or obesity and established cardiovascular disease but without diabetes, found that semaglutide 2.4 mg reduced the risk of major adverse cardiovascular events (MACE) by 20% compared to placebo over a median follow-up of about 40 months. MACE was defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The trial results were published in the New England Journal of Medicine in November 2023.
The new analysis, presented on September 24 and published in a journal, used statistical mediation analysis to determine how much of the cardiovascular benefit was attributable to weight loss versus other mechanisms. According to the researchers, the reduction in MACE was only partially explained by the amount of weight lost, suggesting that semaglutide has direct cardiovascular effects independent of weight reduction.
Possible mechanisms include anti-inflammatory effects, improvement in endothelial function, and reduction in blood pressure and lipid levels, though these are not fully understood. The analysis found that for every 1% of body weight lost, the risk of MACE decreased by a certain percentage, but the overall effect was greater than what would be expected from weight loss alone.
Implications for patients and prescribing
The study authors conclude that semaglutide should be considered a cardiovascular disease reduction drug, which could influence clinical guidelines and prescribing practices. This comes amid growing demand for semaglutide and other GLP-1 drugs for weight loss, which has led to supply shortages and increased scrutiny of their cost and accessibility. The FDA has approved semaglutide for cardiovascular risk reduction in adults with overweight or obesity and established cardiovascular disease, based on the SELECT trial.
The new analysis adds to the understanding of how semaglutide provides cardiovascular benefits. The research was funded by Novo Nordisk, the manufacturer of semaglutide.
The findings were announced on September 24 and are considered preliminary until published in a peer-reviewed journal, although the SELECT trial itself was peer-reviewed. The implications for patients and healthcare providers are significant, as they may lead to broader use of semaglutide for cardiovascular prevention, even in patients without diabetes. However, the drug also carries potential side effects, including nausea, vomiting, diarrhea, and a risk of pancreatitis and gallbladder disease.
The cost of semaglutide remains high, with a monthly list price of approximately $1,349 for Wegovy in the US, although insurance coverage varies. The new analysis is expected to stimulate further research into the mechanisms of GLP-1 receptor agonists and their effects on cardiovascular health. Consult your doctor for medical advice.
