SOUL: Oral Semaglutide Cuts CV Events in Diabetic Patients

An oral formulation of semaglutide, taken daily, is more effective at reducing the risk of major adverse cardiovascular events than traditional therapy alone in patients with diabetes and established CVD and/or chronic kidney disease (CKD), according to top-line results from the SOUL trial.

In announcing the results, Novo Nordisk said Rybelsus, an oral glucagon-like peptide-1 (GLP-1) receptor agonist already approved for insufficiently controlled diabetes to improve glycemic control when added to diet and exercise, reduced the composite of CV death, nonfatal MI, and nonfatal stroke by 14% compared with placebo in the 9,650-patient international trial.

The majority of patients enrolled in SOUL were taking metformin and about 70% had CAD, 42% had CKD, 21% had cerebrovascular disease, and 15.7% had symptomatic PAD. Additionally, nearly one-quarter had heart failure and 49% were taking an sodium-glucose cotransporter 2 (SGLT2) inhibitor at some point during the trial.

Participants were randomized to oral semaglutide 14 mg once daily or placebo in addition to standard of care. In a press release, Novo Nordisk said the regimen “appeared to have a safe and well-tolerated profile in line with previous oral semaglutide trials.” Follow-up is planned for 5 years or longer.

On the basis of these results, which are expected to be presented at a scientific conference in 2025, Novo Nordisk said it plans to file for a label expansion for Rybelsus with both the US Food and Drug Administration and the European Medicines Agency by early next year.

In March 2024, injectable semaglutide (Wegovy; Novo Nordisk) gained an indication for MACE reduction in nondiabetic patients with established CVD and either overweight or obesity based on the results of the SELECT trial. The earlier FLOW trial in diabetic patients with kidney disease had been terminated after an interim analysis showed a drastic reduction in adverse events including MACE in patients taking injectable semaglutide.