An expanded indication for Rybelsus (semaglutide) tablets has been approved by the US Food and Drug Administration (FDA), now allowing the Novo Nordiskmedication to reduce the risk of major adverse cardiovascular events (MACE)—such as CV death, heart attack, or stroke—in high-risk adults with type 2 diabetes, a first for an oral GLP-1 medicine.

Originally approved in 2019 to improve glycemic control as an adjunct to diet and exercise, this new approval underscores the powerful cardiovascular benefits of the semaglutide molecule, which can now be used for both primary and secondary prevention of MACE. The new indication is based on the findings from the phase 3b SOUL trial, a large-scale, placebo-controlled study involving 9,650 participants with type 2 diabetes at high cardiovascular risk.

The SOUL trial demonstrated that oral semaglutide 14 mg, when added to standard therapy, led to a statistically significant 14% relative reduction in the risk of MACE compared to placebo over a four-year period. This significant outcome reinforces the clinical need for therapies that address cardiovascular risk beyond just blood sugar management in this patient population, regardless of whether they have a history of a previous CV event. The overall safety profile observed in the SOUL trial was consistent with previous studies. While Rybelsus was associated with a higher incidence of gastrointestinal disorders, such as nausea, vomiting, and diarrhea, than placebo, the most common serious adverse events overall were cardiac disorders and infections, and serious adverse events were less common in the semaglutide group than in the placebo group. As the only FDA-approved oral GLP-1 therapy, this milestone establishes a new benchmark in cardiometabolic care and highlights Novo Nordisk's commitment to providing innovative, versatile treatment options for people living with chronic disease.