The reduction in risk of CV events, the first to be shown by an antiobesity drug, was higher than expected and could help alter perceptions of the agents as "lifestyle drugs."
The antiobesity medication semaglutide 2.4 mg, marketed as Wegovy® by Novo Nordisk, reduced the risk of major adverse cardiovascular events (MACE) by 20% in adults with overweight or obesity and established cardiovascular disease (CVD).1
The long-anticipated findings from the late-stage landmark SELECT trial were reported on Tuesday morning by Novo Nordisk in a statement that described the trial as a comparison between a once-weekly injection of semaglutide 2.4 mg and placebo as an adjunct to standard of care for prevention of MACE in participants followed for up to 5 years. The cohort of 17 604 participants aged ≥45 years had a BMI ≥27 kg/m2 and CVD but had no history of type 2 diabetes (T2D).
The SELECT trial’s primary endpoint was the composite outcome of the first occurrence of MACE which investigators defined as CV death, nonfatal myocardial infarction, or nonfatal stroke, according to the statement. The study reported a “statistically significant and superior reduction” in MACE of 20% among participants who received the glucagon like peptide 1 (GLP-1) receptor agonist vs those who received placebo. Reduction in risk of all 3 MACE components contributed to the overall superior outcome, according to Novo Nordisk although specific values for each were not included in the announcement of top-line findings.1
Semalgutide is the first antiobesity medication to demonstrate a CV benefit reprising its position as the first GLP=1 receptor agonist to be approved for chronic weight management.
The company says it expects to file for regulatory approval for a label expansion in the US and EU this year and that the full findings from SELECT will be presented at a scientific meeting before year end.1
"People living with obesity have an increased risk of cardiovascular disease but to date, there are no approved weight management medications proven to deliver effective weight management while also reducing the risk of heart attack, stroke or cardiovascular death," said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “SELECT is a landmark trial and has demonstrated that semaglutide 2.4 mg has the potential to change how obesity is regarded and treated.”1
According to reporting on Reuters,2 Medicare, the US health insurance program for adults aged ≥65 years “classifies weight loss treatments as lifestyle drugs.”
In a report published today by CNN,3 an endocrinologist expressed hope that these findings might help improve insurance coverage for the antiobesity medication which costs $1349 a month without insurance.3 “If the SELECT study is positive, it will add to the growing body of evidence that weight loss is not just cosmetic and will encourage insurers to pay for medications that reduce weight,” Willa Hsueh, MD, director of the Diabetes and Metabolism Research Center at Wexner Medical Center at The Ohio State University, told CNN before the results were released.3
Both outlets reported that the 20% reduction in risk of MACE is higher than the 15% to 17% expected by analysts and experts.2,3
Semaglutide 2.4 mg in June 2021 was the first GLP-1 receptor agonist approved in the US as as an adjunct to dietary change and increased exercise for chronic weight management in adults with obesity BMI ≥30 kg/m2 or with overweight (BMI ≥27 kg/m2) and one weight-related comorbidity; it was later approved for children aged ≥12 years with an initial BMI at ≥95th percentile standardized for age and sex.1 The first approval of the incretin mimetic was in 2017 at a dose of 0.5 mg to 1.0 mg as an adjunct to diet and exercise to lower hyperglycemia in persons with T2D. Novo Nordisk was granted a label expansion soon afterward for dose of 2.0 mg for persons with T2D whose hyperglycemia remained uncontrolled by other agents.1