A recent clinical trial has discovered that the drug semaglutide, marketed as Ozempic and Wegovy, is effective in reducing cardiovascular risk in overweight individuals without diabetes. Previously, semaglutide was primarily used to improve blood glucose control in adults with type 2 diabetes. In 2021, it was approved by the FDA as a weight management medication for overweight and obese adults. The drug has shown to reduce cardiovascular risk in overweight or obese individuals with diabetes by improving glucose levels, lowering blood pressure and cholesterol levels, and reducing inflammation. Now, a new study funded by Novo Nordisk, the drug’s developer, conducted by researchers from the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, found that semaglutide can also reduce cardiovascular risk in overweight non-diabetics.
The study marks a significant breakthrough in treating obesity-related cardiovascular complications, as reducing cardiovascular disease has conventionally involved treating high cholesterol, high blood pressure, and diabetes. However, the concept of treating obesity itself to reduce cardiovascular complications has lacked sufficient evidence from lifestyle or pharmacologic intervention studies for overweight or obesity to improve cardiovascular outcomes. This trial is the first to demonstrate that pharmacologic intervention in the form of semaglutide successfully reduces the risk of cardiovascular events in overweight or obese individuals.
The trial enrolled 17,604 patients aged 45 or older from 41 countries who had preexisting cardiovascular disease and a BMI of 27 or greater but no history of diabetes. The patients were randomly assigned to receive a once-weekly subcutaneous injection of 2.4 mg of semaglutide or a placebo. Alongside semaglutide or the placebo, the patients received standard-of-care treatment for cardiovascular disease, including medications to lower cholesterol, blood pressure, and prevent clotting. It is noteworthy that the dosage of semaglutide used in the trial was higher than the dosage used to treat type 2 diabetes.
Over the course of the average 40-week trial, patients treated with semaglutide experienced an average weight loss of 9.4% of their body weight. In comparison, 8.0% of patients receiving the placebo died from cardiovascular causes, nonfatal heart attack, or nonfatal stroke, while only 6.5% of patients taking semaglutide experienced these events—a 20% reduction in relative risk. The reduction in risk was consistent across genders, ethnicities, ages, and baseline levels of body weight. Although no serious safety concerns were observed, gastrointestinal side effects like nausea and diarrhea led to 16.6% of patients on semaglutide discontinuing the trial, compared to 8.2% of patients on the placebo. These side effects are common with glucagon-like peptide-1 (GLP-1) receptor agonists like semaglutide. Additionally, there was a slightly higher rate of gallbladder disorder in the semaglutide group compared to the placebo group, 2.8% versus 2.3%, respectively. Severe gastrointestinal disorders, pancreatitis, kidney injury, and psychiatric disorders were not associated with the drug.
However, some members of the medical community have advised caution when interpreting the trial results. While the findings are promising, it is essential to avoid overinterpretation due to the relatively modest effects observed, stated Dr. Garron Dodd from the University of Melbourne. The mechanisms through which semaglutide protects against cardiovascular-related death remain unclear, and questions arise regarding whether the observed benefits are solely due to weight loss, given the 8.5% greater reduction in body weight in the semaglutide-treated group. The focus of the study on patients with mild or stage 1 obesity (average BMI around 33) also raises concerns about the applicability of these effects to severely obese patients. Although previous studies have shown that some GLP-1 receptor agonist medications, including semaglutide, can reduce the risk of cardiovascular events in individuals with diabetes, it was not previously clear if the reduced risk was primarily due to improved blood glucose control. This study is significant as it is the first clinical trial to demonstrate that this type of medication can reduce the risk of cardiovascular events in both diabetes and weight management.
One limitation of the trial is that it only included patients with preexisting cardiovascular disease. Further studies are necessary to determine the effects of semaglutide on overweight or obese individuals without cardiovascular disease. The growing recognition that obesity and overweight are metabolic diseases highlights the need for effective therapies, emphasized Michael Lincoff, the lead author of the study. The trial results demonstrate the effectiveness of semaglutide in reducing the excess risk associated with obesity and potentially deadly cardiovascular complications.
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1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it
