After clearing Novo Nordisk’s semaglutide treatments Ozempic and Wegovy to reduce the risk of major adverse cardiovascular events (MACE), the FDA has followed suit with a MACE expansion for its semaglutide pill Rybelsus.
The approval is good news for Type 2 diabetes patients who prefer Novo’s GLP-1 tablets to its injected versions. It also establishes a standard for oral drugs that are currently in development in the arena, according to Novo Nordisk’s U.S. operations chief Dave Moore.
"As the only FDA-approved GLP-1 therapy in a pill, now recognized for its proven cardiovascular benefits, a new benchmark has been set for future oral innovations,” Moore said in a release. “The semaglutide molecule has consistently demonstrated robust outcomes across multiple, large-scale trials, further reinforcing the already established cardiovascular profile it delivers for patients.”
The FDA signed off on Rybelsus tablets at 7 mg and 14 mg to reduce the risk of cardiovascular death, heart attack, or stroke in adults with Type 2 diabetes who are at a greater risk of these events. The approval comes five weeks after the European Medicines Agency expanded the use of Rybelsus to the same group of patients.
The approval was based on a phase 3 trial of 9,650 adults who have Type 2 diabetes with established cardiovascular disease or chronic kidney disease. The primary endpoint was the time to first occurrence of a MACE event, which includes cardiovascular death, nonfatal myocardial infarction or nonfatal stroke.
According to the findings, the 14 mg dose of Rybelsus reduced the risk of MACE by 14% compared to placebo. With a follow-up duration of four years, MACE occurred in 12% of patients on Rybelsus compared to 13.8% of those on placebo.
Adverse events that led to discontinuation occurred in 749 participants (15.5%) in the Rybelsus group and in 559 participants (11.6%) in the placebo group—most of those dropping out had gastrointestinal disorders.
While Rybelsus is overshadowed by Novo’s mega-blockbusters Ozempic and Wegovy, it did generate 11.3 billion Danish kroner ($1.7 billion) in the first half of this year.
Rybelsus was originally approved in 2019 for Type 2 diabetes patients who were not achieving their A1C goal with other antidiabetic treatments. In 2023, the FDA allowed its use as a first-line treatment for Type 2 diabetes. Novo is also testing Rybelsus as a treatment to reduce the risk of heart failure.
Ozempic and Wegovy gained their MACE nods in 2024 and 2020, respectively. Meanwhile, Novo’s primary rival in the market, Eli Lilly, has yet to secure a MACE approval for its dual-action tirzepatide products.
The Indianapolis company is testing obesity treatment Zepbound in the phase 3 Surmount-MMO trial. Three months ago, Lilly showed results from the phase 3 Surpass-CVOT study, which demonstrated Mounjaro’s non-inferiority to its GLP-1 Trulicity in reducing the risk of MACE.
Though analysts considered the results underwhelming, Lilly plans to submit Mounjaro for approval to reduce the risk of MACE by the end of this year.