The U.S. Food and Drug Administration approved oral semaglutide (Rybelsus) to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes who are at high cardiovascular risk, including those without a prior cardiovascular event. This expands Rybelsus’ indication beyond glycemic control, marking the first approval of an oral glucagon-like peptide-1 (GLP-1) receptor agonist for cardiovascular risk reduction.

In the phase 3b SOUL trial, oral semaglutide 14 mg, in addition to standard therapy, reduced the risk of major adverse cardiovascular events—defined as cardiovascular (CV) death, nonfatal myocardial infarction, or nonfatal stroke—by 14% compared with placebo. The relative reduction translated to an absolute risk reduction of 2% at 3 years. Serious adverse events occurred in 47.9% of patients receiving semaglutide and 50.3% receiving placebo. Gastrointestinal events were the most common cause of discontinuation.

Rybelsus is now indicated for both primary and secondary prevention of CV events in adults with type 2 diabetes (T2D) who are at high risk. It remains the only U.S. Food and Drug Administration-approved oral GLP-1 receptor agonist available in 7 mg and 14 mg formulations, administered once daily as an adjunct to diet and exercise.

The SOUL trial was a multicenter, randomized, double-blind, placebo-controlled study enrolling 9,650 adults with T2D at high CV risk. Over a mean follow-up of 4 years, major adverse cardiovascular events occurred in 12.0% of participants receiving semaglutide compared with 13.8% of those on placebo. The safety profile was consistent with prior semaglutide studies with gastrointestinal disorders among the most common adverse effects.

Rybelsus was first approved in 2019 to improve glycemic control in adults with T2D. Novo Nordisk has also submitted a supplemental U.S. application for a once-daily oral semaglutide formulation under the Wegovy brand for obesity management, with a decision expected later this year.

Source: Novo Nordisk