FDA Reviews Novo Nordisk's Bid to Expand Rybelsus for Cardiovascular Risk Reduction

The U.S. Food and Drug Administration (FDA) has accepted Novo Nordisk's application to expand the label for its oral GLP-1 treatment, Rybelsus (semaglutide), to include the reduction of major adverse cardiovascular events (MACE) in adults with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD).

SOUL Trial Results Support Label Extension

Novo Nordisk's application is backed by data from the phase 3 SOUL trial, which enrolled 9,650 adults with type 2 diabetes and ASCVD and/or CKD. The study demonstrated that a daily 14 mg dose of Rybelsus reduced the risk of MACE by 14% compared to placebo. Specifically, 579 patients on Rybelsus experienced MACE versus 668 on placebo.

Dr. John Buse, co-chair of the SOUL trial steering committee, emphasized the significance of these findings, stating, "The significant reduction in risk of composite endpoint of heart attack, stroke, or death seen in the SOUL trial in adults with type 2 diabetes highlights the cardiovascular impact of oral semaglutide."

The safety profile of Rybelsus in the SOUL trial was consistent with previous studies, with no new safety signals observed. Serious adverse events (SAEs) were slightly less frequent in the Rybelsus group (48%) compared to placebo (50%). However, gastrointestinal disorders were more common with Rybelsus (5%) than placebo (4.4%), and adverse events leading to treatment discontinuation were higher for Rybelsus (15.5%) than placebo (11.6%).

Expanding Novo Nordisk's Cardiometabolic Portfolio

The potential label expansion for Rybelsus aligns with Novo Nordisk's broader strategy to address cardiometabolic diseases. Dr. Michael Radin, Novo's director of diabetes medical affairs, noted, "Novo Nordisk continues to evolve its leadership beyond any one therapy area, toward a broader spectrum of cardiometabolic diseases that explores the interconnectivity of these conditions."

Rybelsus, approved for type 2 diabetes in 2019, has established a significant market presence despite being overshadowed by its injectable counterparts, Ozempic and Wegovy. In 2024, Rybelsus generated revenue of 23.3 billion Danish kroner ($3.4 billion), while Ozempic and Wegovy combined for sales of 152 billion Danish kroner ($22 billion).

Novo Nordisk has already secured FDA approvals for its injectable semaglutide products in cardiovascular risk reduction. Ozempic was approved in 2020 to reduce the risk of MACE in patients with type 2 diabetes and cardiovascular disease, demonstrating a 26% risk reduction. More recently, in January 2025, Ozempic received FDA approval to reduce the risk of worsening kidney disease and cardiovascular death in patients with type 2 diabetes and CKD, based on a trial showing a 24% risk reduction.

Additionally, Wegovy, Novo Nordisk's weight loss treatment, recently demonstrated promising results in cardiovascular risk reduction. The SCORE study, a retrospective observational study presented at the American College of Cardiology's Annual Scientific Session, showed that Wegovy was associated with a 57% lower risk of MACE in patients with cardiovascular disease who are overweight or obese.

As Novo Nordisk continues to expand its cardiometabolic portfolio, the company is also exploring semaglutide's potential in other indications, including metabolic dysfunction-associated steatohepatitis (MASH), heart failure, and Alzheimer's disease.