Semaglutide (Wegovy) Receives FDA Label Expansion to Include Cardiovascular Risk Reduction

Credit: US Food and Drug Administration

The US Food and Drug Administration has approved an expanded label indication for semaglutide 2.4 mg (Wegovy) to include reducing the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease and obesity or overweight.

Announced on March 08, 2024, the approval marks the first time the FDA had approved a treatment for reducing cardiovascular risk specifically for patients with overweight or obesity and is based on data from the landmark SELECT trial.¹

“Wegovy is now the first weight loss medication to also be approved to help prevent life-threatening cardiovascular events in adults with cardiovascular disease and either obesity or overweight,” said John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research.¹ “This patient population has a higher risk of cardiovascular death, heart attack and stroke. Providing a treatment option that is proven to lower this cardiovascular risk is a major advance for public health.”

Semaglutide, unlike any other agent in recent decades, has captured the attention of the medical community and general public in recent years, driven primarily by revelations surrounding its potential in chronic weight management. Following a historic approval in 2021 based on data from the STEP trial, care providers waited with bated breath for the results of the SELECT trial, which compared use of semaglutide 2.4 mg against placebo therapy for a composite cardiovascular outcome comprised of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke.^1,2

A 17,604-patient trial, SELECT randomized patients in a 1:1 ratio and had a median duration of follow-up of 39.8±9.4 months. For inclusion in the trial, patients needed to be 45 years of age or older, have preexisting cardiovascular disease, and have a BMI of 27 or greater but no history of diabetes.²

Results of the trial, which were presented at the American Heart Association’s 2023 annual scientific sessions, demonstrated use of the GLP-1 receptor agonist was associated with a 20% relative reduction in risk of a primary endpoint event, with events occurring among 6.5% of the semaglutide group and 8.0% of the placebo group (HR, 0.80; 95% Confidence interval [CI], 0.72 to 0.90; P <.001).²

Analysis of weight loss in the trial revealed a mean change in body weight of –9.39% with semaglutide and –0.88% with placebo (estimated treatment difference, –8.51 percentage points; 95% CI, –8.75 to –8.27). Further analysis of the trial pointed to nonsignificant trends towards benefit for cardiovascular death (HR, 0.85; 95% CI, 0.71 to 1.01; P=.07), heart failure hospitalization or urgent medical visit (HR, 0.82; 95% CI, 0.71 to 0.96), all-cause mortality (HR, 0.81; 95% CI, 0.71 to 0.93), an HbA1c of 6.5% or greater (HR, 0.27; 95% CI, 0.24 to 0.31).²

According to a release form Novo Nordisk, the company has also filed for a label expansion in the European Union and a decision on that application is expected later in 2024. Additionally, the company highlighted the label for semaglutide 2.4 mg will now include data from SELECT showing a risk reduction in cardiovascular death by 15% and a risk reduction of death from any cause by 19% relative to placebo.³

"We are very pleased that Wegovy is now approved in the US as the first therapy to help people manage their weight and reduce cardiovascular risks," said Martin Holst Lange, executive vice president and head of Development at Novo Nordisk.³ “This approval is an important milestone for people living with obesity and cardiovascular disease, as the SELECT data demonstrated that Wegovy has the potential to prolong lives by addressing some of the leading causes of preventable deaths by reducing the risks of cardiovascular events.”

References:

1. _{^{Office of the Commissioner. FDA approves first treatment to reduce risk of serious heart problems specifically in adults with obesity or overweight. U.S. Food and Drug Administration. March 8, 2024. Accessed March 8, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-reduce-risk-serious-heart-problems-specifically-adults-obesity-or.}}
2. _{^{Campbell P. Semaglutide 2.4 mg (Wegovy) reduces cardiovascular risk in overweight/obesity with CVD. HCP Live. November 11, 2023. Accessed March 8, 2024. https://www.hcplive.com/view/semaglutide-2-4-mg-wegovy-reduces-cardiovascular-risk-in-overweight-obesity-with-cvd.}}
3. _{^{Wegovy® approved in the US for cardiovascular risk reduction in people with overweight or obesity and established cardiovascular disease. Novo Nordisk. March 8, 2024. Accessed March 8, 2024. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=167030.}}