FDA Approves Expanded Indication for Wegovy to Lower Cardiovascular Risk in Adults with Heart Disease, Obesity

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The FDA has expanded the indication of Novo Nordisk’s Wegovy (semaglutide) for lowering the risk of major adverse cardiovascular events (MACE) in adults with known heart disease and with either obesity or overweight, in addition to a reduced calorie diet and increased physical activity.¹

Wegovy, a glucagon-like peptide-1 (GLP-1) receptor agonist, was initially approved in June 2021 for chronic weight management in those with obesity or overweight and at least one weight-related condition, including high blood pressure, type 2 diabetes, or high cholesterol, in addition to diet and increased exercise. Semaglutide 1 mg injection (Ozempic) was initially approved to treat type 2 diabetes in 2017.²

"Today, we're taking a pivotal step forward in addressing some of the most pressing health issues of our time with the added indication for Wegovy," Doug Langa, executive vice president, head of North America Operations, and president of Novo Nordisk, said in a press release. "We recognize how important this moment is for the millions of people who live with excess weight or obesity and known heart disease, and we will continue to advance options that put their needs first. Reducing this risk is a key part of our commitment to driving change for this community, as we work to increase manufacturing capacity to responsibly supply this important medicine.”¹

The regulatory action was based on findings from the landmark, multicenter, randomized, double-blind, placebo-controlled, event-driven Phase III SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) trial. The study analyzed the efficacy of Wegovy at a dose of 2.4 mg compared with placebo as an adjunct to standard of care for lowering the risk of MACE in individuals with established cardiovascular disease and with overweight or obesity, as well as no prior history of diabetes. Investigators enrolled 17,604 adults across 41 countries at more than 800 investigator sites.

Trial data show that Wegovy significantly lowered the risk of first occurrence of a three-part composite MACE endpoint, which was comprised of cardiovascular death, non-fatal heart attack, or non-fatal stroke. The trial’s primary composite outcome occurred in 6.5% of those administered Wegovy and 8.0% in the placebo cohort.

The estimated relative risk reduction of MACE was 20% compared with placebo (HR 0.80 [95% CI: 0.72, 0.90] p <0.001, absolute risk reduction of 1.5% at 40 months, the mean follow-up duration). MACE reduction with Wegovy was not affected by age, sex, race, ethnicity, baseline body mass index, or impaired renal function, according to the study.

In terms of safety, 16% of patients administered Wegovy discontinued treatment because of an adverse event (AE) compared to 8% in the placebo cohort. The most common AE causing discontinuation was gastrointestinal disorders, which was reported in 10% of patients in the Wegovy cohort and 2% in the placebo cohort.

Wegovy includes a boxed warning to inform healthcare professionals and patients regarding a potential risk of thyroid C-cell tumors. The GLP-1 receptor agonist should not be administered to those with a personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2.²

In addition to the latest approval, Wegovy is also indicated for individuals aged 12 years and older with obesity, or adults with overweight and weight-related medical problems, to lose excess weight combined with a reduced calorie diet and increased physical activity.

"This approval is a significant decision because people living with excess weight or obesity and established cardiovascular disease and without diabetes have never had an FDA-approved treatment option that lowers weight and reduces the likelihood of another cardiovascular event,” SELECT lead study author A. Michael Lincoff, MD, professor of Medicine at Cleveland Clinic, said in a press release. "For healthcare professionals, this approval provides a new treatment option to help us address cardiovascular residual risk that remains for patients on current standard of care.”¹

References

1. Wegovy® receives FDA approval for cardiovascular risk reduction in adults with known heart disease and overweight or obesity. Novo Nordisk. News release. March 8, 2024. Accessed March 8, 2024. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=167031

2. FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014. FDA. News release. June 4, 2012. Accessed March 8, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014