EU approves Novo Nordisk’s oral semaglutide

The European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has approved an update to Novo Nordisk’s Rybelsus (oral semaglutide) label to reflect the cardiovascular benefits seen in the SOUL trial. As a result, Rybelsus is now the first and only oral glucagon-like peptide 1 receptor agonist (GLP-1 RA) – mimicking a natural hormone in your body that helps regulate blood sugar, appetite, and digestion – available in the EU for type 2 diabetes with a proven cardiovascular benefit.

SOUL was a multicentre, international, randomised, double-blind, parallel-group, placebo-controlled, phase 3 cardiovascular outcomes trial, with 9,650 participants enrolled. It was conducted to assess the effect of oral semaglutide versus placebo, when added to standard of care, on cardiovascular outcomes in people with type 2 diabetes and established cardiovascular disease and/or chronic kidney disease (CKD). The SOUL trial was initiated in 2019. The primary outcome was time-to-first occurrence of major adverse cardiovascular events (MACE; a composite objective consisting of cardiovascular death, heart attack and stroke).

The SOUL trial demonstrated a superior reduction in MACE of 14% for people treated with oral semaglutide compared to placebo in people with type 2 diabetes and cardiovascular disease and/or CKD, making Rybelsus (oral semaglutide) the first and only oral GLP-1 RA with a proven cardiovascular benefit.

“Heart problems are the leading cause of disability and death for people living with type 2 diabetes. Therefore, treatments that also address heart problems are key to improving not only health outcomes, but also quality of life – and this approval will help do just that,” said Emil Kongshøj Larsen, executive vice president, International Operations at Novo Nordisk. “This milestone makes semaglutide the only oral GLP-1 RA with proven blood glucose and body weight reduction, as well as cardiovascular benefits.”

New results from the SOUL trial will presented at the European Association for the Study of Diabetes (EASD) 2025 Annual Meeting, 15–19 September. These include findings that treatment with oral semaglutide significantly reduced hospitalisations related to serious adverse events compared with placebo. Additional SOUL results will be presented at the same meeting, which highlight that the cardiovascular benefits of oral semaglutide were consistent regardless of body mass index (BMI) and body weight of participants.

In the US, a decision is expected later this year for a label extension for the cardiovascular indication for Rybelsus. Novo Nordisk has also submitted an application in the US for a once-daily 25 mg oral formulation of semaglutide (Wegovy in a pill) in adults living with obesity or overweight and cardiovascular disease. A decision is expected at the turn of this year, and if approved, Wegovy would become the first oral GLP-1 RA indicated for chronic weight management.

Rybelsus is the first and only oral GLP-1 RA approved for the treatment of type 2 diabetes, following its launch in 2019. It is supported by a strong clinical and real-world evidence base, demonstrating superior blood glucose reduction and body weight reduction versus multiple comparators, as well as an established safety profile in people with type 2 diabetes.