Novo Nordisk presented the full results from the SOUL cardiovascular outcomes trial, demonstrating that Rybelsus (oral semaglutide) significantly reduced the risk of major adverse cardiovascular events in adults with type 2 diabetes and cardiovascular disease (CVD) and/or chronic kidney disease (CKD). These new data from the phase 3b trial were featured during a late-breaking clinical trial session at the American College of Cardiology’s (ACC) Annual Scientific Session and Expo in Chicago, US and simultaneously published in New England Journal of Medicine. The SOUL trial achieved its primary endpoint, demonstrating a 14% reduction in risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes and CVD and/or CKD when treated with Rybelsus compared to placebo.
Each component of MACE, being CV death, nonfatal myocardial infarction and nonfatal stroke, contributed to the risk reduction.?Heart attacks and strokes are the leading causes of disability and death for people with type 2 diabetes, and there is a need for new, patient-centric treatments to help manage this risk,? said Darren McGuire, MD, Distinguished Chair in Cardiovascular Science and Teaching Professor of Medicine at UT Southwestern, US, and SOUL steering committee co-chair. ?The SOUL trial in adults with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) and/or CKD demonstrated significant reductions in the risk of major cardiovascular events including heart attack, stroke and CV death in those treated with oral semaglutide vs placebo.
The proven cardiovascular benefit reflects a profound clinical impact for patients who now have an oral option to improve health outcomes.?Cardiometabolic diseases span a wide range of conditions, including cardiovascular and peripheral artery disease, type 2 diabetes and chronic kidney disease. When combined, these conditions represent the leading cause of death globally. Having type 2 diabetes directly increases the risk of developing interconnected cardiometabolic diseases, while also contributing to the progression of other cardiovascular risk factors.
Nearly one in three adults with type 2 diabetes have CVD. The overall safety profile of oral semaglutide in SOUL was consistent with that seen in previous semaglutide 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.
The most common SAEs were cardiac disorders (17.8% and 19.8%, respectively) and infections/infestations (15.0% and 16.5%, respectively) in the Rybelsus and placebo arms. In a key secondary analysis from SOUL published simultaneously, oral semaglutide reduced risk of MACE independently of baseline use of SGLT2i and suggests similar benefits in participants with and without concomitant SGLT2i use during trial.SOUL confirmed the well-established safety and tolerability profile of semaglutide supported by long-term safety data with more than 33 million patient years.Based on data from the SOUL clinical trial, Novo Nordisk submitted a label extension application for Rybelsus, which has been accepted for review by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA. A decision is anticipated in 2025.
