Oral semaglutide reduces major cardiovascular event risk by 14% in type 2 diabetes (SOUL trial)

On October 21, 2024, Novo Nordisk revealed the headline findings from the SOUL cardiovascular outcomes trial conducted in Bagsvaerd, Denmark. This double-blinded, randomized study examined the efficacy of oral semaglutide compared to a placebo, both implemented alongside standard care, with the aim of preventing major adverse cardiovascular events (MACE).

The trial involved 9,650 participants who had type 2 diabetes coupled with either established cardiovascular disease (CVD) or chronic kidney disease (CKD). During the trial, 49% of patients were treated with SGLT2 inhibitors as part of the standard care regimen.

The primary goal of the study was met, demonstrating that oral semaglutide significantly reduced the incidence of MACE by 14% compared to the placebo. MACE in this context was defined as the composite measure of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Each element of this composite measure contributed to the observed reduction, underscoring the effectiveness of oral semaglutide.

Safety and tolerability of oral semaglutide remained consistent with prior trials, indicating it is well-tolerated by patients. Martin Holst Lange, executive vice president and head of Development at Novo Nordisk, expressed satisfaction with the results, highlighting the importance of therapies that can simultaneously address type 2 diabetes and cardiovascular disease. He emphasized that approximately one-third of adults with type 2 diabetes also suffer from cardiovascular conditions, making it crucial to develop therapies tackling both illnesses.

Novo Nordisk intends to seek regulatory approval for an expanded label for Rybelsus in both the United States and Europe around the end of the year. The detailed outcomes of the SOUL trial are anticipated to be presented at a scientific conference in 2025.

The SOUL trial, initiated in 2019, was a multicenter, international, randomized, double-blind, parallel-group, placebo-controlled phase 3 study. Its primary purpose was to assess the impact of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established CVD and/or CKD. Participants were randomly assigned to receive either oral semaglutide or a placebo, with both groups receiving standard care.

Rybelsus, the brand name for oral semaglutide, is approved for daily administration in three doses: 3 mg, 7 mg, and 14 mg. It is prescribed to adults with inadequately controlled type 2 diabetes to enhance glycemic control, in conjunction with diet and exercise. In the European Union, a new formulation offering 1.5 mg, 4 mg, and 9 mg doses has been approved, demonstrating bioequivalence to the original formulation.

Novo Nordisk, established in 1923 and headquartered in Denmark, is a prominent global healthcare company focused on addressing serious chronic diseases. The company is dedicated to scientific innovation and enhancing access to medicine, with the ultimate goal of preventing and curing diseases. Novo Nordisk employs approximately 69,000 people across 80 countries and distributes its products in around 170 countries. The company’s B shares are listed on Nasdaq Copenhagen, and its ADRs are traded on the New York Stock Exchange.