Rybelsus Reduces Cardiovascular Risk by 14% in New Trial | ACC 2025

Rybelsus, the oral semaglutide product approved to treat type 2 diabetes, reduced the risk of major adverse cardiovascular events (MACE) by 14% compared with placebo in adults with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) and/or chronic kidney disease (CKD). These new data from a phase 3 trial were featured during a late-breaking clinical trial session today at the American College of Cardiology’s (ACC) Annual Scientific Session and Expo.

Based on data from the SOUL clinical trial, Novo Nordisk submitted a label extension application for Rybelsus tablets 14 mg, which has been accepted for review by the FDA. A decision is anticipated in 2025.

Rybelsus is available in both 7 mg and 14 mg and has a list price of $997.58 per package. People with commercial insurance may pay as little as $10 for a one-, two- or three month prescription.

Novo Nordisk also markets two other semaglutide products: Wegovy to treat obesity and Ozempic to treat type 2 diabetes. In January 2025, the FDA approved Ozempic to reduce the risk of kidney disease worsening, kidney failure, and death due to cardiovascular disease in adults with type 2 diabetes and chronic kidney disease.

Sales of Wegovy, Ozempic and Rybelsus increased 27% to $39.4 billion in 2024, according to the company. Sales of Wegovy alone grew 57% to $9.4 billion.

The three semaglutide drugs are at the top of CMS's next 15 Medicare Part D drugs to be subject to price negotiations as part of the Inflation Reduction Act. Negotiations with participating drug companies begin this year, and the new prices will become effective in 2027. The three semaglutide products had total Part D gross costs of $14.4 billion from November 2023 to October 2024, according to CMS.

In the SOUL trial, 9,650 adults over the age of 50 with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease were enrolled. Investigators wanted to assess Rybelsus 14 mg compared with placebo on cardiovascular outcomes. They used a three-point composite endpoint consisting of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke compared with placebo.

Investigators found that Rybelsus 14 mg demonstrated a 14% reduction in the risk of major adverse cardiovascular events. The primary endpoint was time from randomization to first occurrence of a major adverse cardiovascular event, including cardiovascular death, nonfatal myocardial infarction or nonfatal stroke.

John B. Buse, M.D., Ph.D.

“Given the cardiovascular outcomes seen in SOUL, the trial represents important data for a community who may need options that also address common and serious comorbidities of type 2 diabetes, like cardiovascular disease,” John B. Buse, M.D., Ph.D., distinguished professor of medicine, director of UNC Diabetes Care Center and NC Translational and Clinical Sciences Institute, and steering committee co-chair of the SOUL trial, said in a news release.

The overall safety profile of Rybelsus in SOUL was consistent with that seen in previous trials, and no new safety signals were observed. The incidence of serious adverse events (SAEs) was lower in participants receiving Rybelsus than those receiving placebo, mostly due to the higher rate of cardiovascular events and infections in the placebo group.

Adverse events leading to permanent treatment discontinuation were more common for Rybelsus than placebo, comprising mainly gastrointestinal disorders in both arms.