A clinical trial has found that the cardiovascular benefits that the drug semaglutide affords to overweight or obese type 2 diabetics extend to those without diabetes as well. The study suggests that the drug offers a new way to reduce the potentially deadly risks associated with obesity and being overweight in non-diabetics.
Semaglutide, sold as Ozempic and Wegovy, started life as a medication to improve blood glucose control in adults with type 2 diabetes, before being approved by the FDA in 2021 for use as a weight management medication in overweight and obese adults. In overweight or obese diabetics, the drug has been shown to reduce cardiovascular risk by improving glucose levels, reducing blood pressure and cholesterol levels, and reducing inflammation.
Now, in a new study funded by Novo Nordisk, the company that developed semaglutide, researchers from the Cleveland Clinic Lerner College of Medicine at Case Western Reserve University have found that the drug is also effective at reducing cardiovascular risk in overweight non-diabetics.
“It is known that overweight and obesity increase a person’s risk of cardiovascular events,” said Michael Lincoff, the study’s lead author. “Yet 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 the lack of evidence that lifestyle or pharmacologic interventions for overweight or obesity improve cardiovascular outcomes. 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.”
The researchers enrolled 17,604 patients from 41 countries aged 45 or over with preexisting cardiovascular disease and a BMI of 27 or greater but no history of diabetes in the trial. Preexisting cardiovascular disease included previous heart attack, stroke and/or peripheral artery disease. Patients were randomly assigned to receive a once-weekly subcutaneous injection of 2.4 mg of semaglutide or a placebo. In addition to receiving either semaglutide or placebo, patients also received standard-of-care treatment for cardiovascular disease, such as cholesterol-lowering, blood pressure and anti-clotting medications. It’s noted that the semaglutide dose given is higher than that given to treat type 2 diabetes.
Over the course of the trial, which ran for an average of 40 weeks, patients treated with semaglutide lost an average of 9.4% of their body weight. Of those receiving the placebo, 8.0% died from cardiovascular causes, nonfatal heart attack, or nonfatal stroke compared to 6.5% of patients taking semaglutide – a 20% reduction in relative risk. The reduction was similar between men and women and across different ethnicities, ages, and baseline levels of body weight.
While no “unexpected safety issues” were observed, gastrointestinal side effects such as nausea and diarrhea caused 16.6% of patients on semaglutide to discontinue the trial, compared with 8.2% taking the placebo. The researchers say these side effects are not uncommon with glucagon-like peptide-1 (GLP-1) receptor agonists like semaglutide. In addition, there was a “slightly higher” rate of gallbladder disorder in the semaglutide group compared to the placebo group, 2.8% versus 2.3%, respectively. The drug was not associated with severe gastrointestinal disorders, pancreatitis, kidney injury or psychiatric disorders.
The trial results have been viewed with cautious optimism by others in the medical community.
“While the findings are exciting, caution must be exercised in interpreting them,” said Dr Garron Dodd, a Laboratory Head and Senior Lecturer at The University of Melbourne. “The observed effects, while statistically significant, are relatively modest, emphasizing the need to avoid overinterpretation. The mechanism through which semaglutide protects against cardiovascular-related death remains unclear, with questions arising about whether the observed benefits are solely attributed to weight loss, given the 8.5% great reduction in body weight in the semaglutide-treated group. Furthermore, the study’s focus on patients with mild or stage 1 obesity (average BMI around 33) prompts scrutiny regarding the potential applicability of these effects in several obese patients.”
“Although some GLP-1 receptor agonist medications (including semaglutide) have previously been shown to reduce the risk of cardiovascular events in people with diabetes, it wasn’t clear until now if the reduced risk was mainly due to the improvement in blood glucose control," added Associate Professor Priya Sumithran, from the Department of Endocrinology and Diabetes at the Alfred Hospital in Melbourne. "This study is important because it is the first clinical trial to show that this type of medication can reduce the risk of cardiovascular events not only when used for diabetes management but also weight management.”
One of the trial’s limitations is that only patients with preexisting cardiovascular disease were included. Further studies are required to ascertain the effect of semaglutide on overweight or obese persons without cardiovascular disease.
“There’s growing recognition that obesity and overweight are really metabolic diseases, and yet, effective therapies have been quite limited,” said Lincoff. “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.”
The study was published in The New England Journal of Medicine.
Source: Cleveland Clinic