FDA Approves Semaglutide to Prevent Heart Events in Patients With CVD and Excess Weight

Semaglutide (Wegovy; Novo Nordisk) gained another indication Friday, as the FDA expanded its approved uses to include prevention of cardiovascular death, myocardial infarction, and stroke in adult patients who have cardiovascular disease (CVD) and overweight or obesity.¹

The new indication was granted after a priority review process and was based on results from the SELECT cardiovascular outcomes trial (NCT03574597).² Findings from SELECT showed that semaglutide significantly reduced the risk of major adverse cardiovascular events (MACE)—cardiovascular death, nonfatal myocardial infarction (heart attack), or nonfatal stroke)—by 20% compared with placebo when added to standard of care.

"This expanded indication is a major step forward in the treatment of obesity and prevention of its cardiovascular consequences," Ian Neeland, MD, told The American Journal of Managed Care® (AJMC®). "It opens the door to expanded access, and hopefully improved insurance coverage, of this important treatment option for millions of people at risk." Neeland serves as director of cardiovascular prevention and co-director of the Center for Integrated and Novel Approaches in Vascular-Metabolic Disease, University Hospitals Harrington Heart & Vascular Institute, and associate professor of medicine at Case Western Reserve University School of Medicine.

Semaglutide was first approved by the FDA in June 2021, when it became the first new drug to receive an approval for chronic weight management since 2014.³ At that time, it was indicated only for chronic weight management in adults with obesity or those with overweight who had at least 1 weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol. In December 2022, the eligible population was expanded to include pediatric patients 12 years or older with a body mass index of at least the 95th percentile for their age and sex.⁴ As with the original approvals, the newly expanded indication specifies that the semaglutide injections should be used in addition to reducing calories and increasing physical activity.¹

The FDA’s news release notes that the multicenter, double-blind SELECT trial randomly assigned more than 17,600 participants to receive either semaglutide or placebo in addition to standard of care therapy for managing their blood pressure and cholesterol, if needed, and counseling on achieving a healthy lifestyle, including diet and activity.¹ Participants were 45 years or older and had an established diagnosis of CVD but no history of diabetes in the past 5 years.²

The MACE end point occurred in 6.5% of participants who received semaglutide vs 8% of those who received placebo.¹ Reductions in MACE risk were seen regardless of baseline age, sex, race, ethnicity, body mass index, or renal function impairment.² In addition to the 20% composite reduction, semaglutide was associated with a 15% reduction in risk of cardiovascular death and a 19% reduction in all-cause death risk vs placebo.²

Wegovy, a 2.4-mg injection, is part of the glucagon-like peptide-1 (GLP-1) receptor agonist class, which also includes 0.5-, 1-, or 2-mg injection semaglutide (Ozempic), approved for glycemic control in adults with type 2 diabetes. Amid increasing use of Ozempic, Wegovy, and semaglutide tablets (Rybelsus) for weight loss, there have been shortages reported in the past year, leaving some individuals with diabetes unable to access the drug.⁵

At the same time, employers and health insurers have been grappling with how to cover and pay for these drugs considering their large population of eligible recipients. On Thursday, Cigna announced the launch of a program through its pharmacy benefit manager unit that would guarantee clients a 15% cap on annual cost increases for these treatments by steering patients toward lifestyle modification and coaching support, representing what it called the “industry’s first financial guarantee” for clients interested in covering GLP-1 receptor agonists.⁶

The prescribing information for semaglutide includes a boxed warning to inform health care professionals and patients about the risk of thyroid C-cell tumors.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,” John Sharretts, MD, director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research, said in the FDA’s news release.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.”

References

1. FDA approves first treatment to reduce risk of serious heart problems specifically in adults with obesity or overweight. News release. FDA. 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. Wegovy® approved in the US for cardiovascular risk reduction in people with overweight or obesity and established cardiovascular disease. News release. Novo Nordisk. March 8, 2024. Accessed March 8, 2024. https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=167030

3. Inserro A. FDA clears semaglutide for weight loss when used with diet, exercise. AJMC. June 4, 2021. Accessed March 8, 2024. https://www.ajmc.com/view/fda-clears-semaglutide-for-weight-loss-when-used-with-diet-exercise

4. FDA approves once-weekly Wegovy injection for the treatment of obesity in teens aged 12 years and older. News release. Novo Nordisk. December 23, 2022. Accessed May 18, 2023. https://www.novonordisk-us.com/media/news-archive/news-details.html?id=151389

5. Klein HE. An ongoing crisis: semaglutide shortage raises dual concerns for obesity and diabetes treatment. AJMC. December 21, 2023. Accessed March 8, 2024. https://www.ajmc.com/view/an-ongoing-crisis-semaglutide-shortage-raises-dual-concerns-for-obesity-and-diabetes-treatment

6. AJMC Staff. What we’re reading: FDA delays decision on donanemab; weight-loss drug costs; effective RSV treatment. AJMC. March 8, 2024. Accessed March 8, 2024. https://www.ajmc.com/view/what-we-re-reading-fda-delays-decision-on-donanemab-weight-loss-drug-costs-effective-rsv-treatment