Oral Semaglutide Shows Significant Cardiovascular Benefits in Type 2 Diabetes Patients: SOUL Trial Results
Cardiometabolic diseases, which encompass a broad spectrum of conditions such as cardiovascular disease, peripheral artery disease, type 2 diabetes, and chronic kidney disease (CKD), remain a leading cause of death worldwide. Addressing this urgent health challenge, Novo Nordisk has unveiled promising findings from its SOUL cardiovascular outcomes trial.
Presented at the American College of Cardiology’s Annual Scientific Session & Expo in Chicago and published in the New England Journal of Medicine, the phase 3b SOUL trial demonstrated that oral semaglutide significantly lowers the risk of major adverse cardiovascular events (MACE) in adults with type 2 diabetes and pre-existing cardiovascular and/or kidney disease.
The study met its primary endpoint, showing a 14% reduction in the risk of MACE—including nonfatal heart attack (26%), nonfatal stroke (12%), and cardiovascular death (7%)—compared to placebo. Remarkably, participants from the Asian region experienced an even greater risk reduction of 27%.
Dr. AG Unnikrishnan, CEO and Chief of Endocrinology at Chellaram Diabetes Institute in Pune, highlighted the trial’s importance, stating, “The SOUL trial has confirmed that oral semaglutide reduces the risk of major cardiovascular events, regardless of whether patients were already on SGLT2 inhibitors. This consistency across treatment groups shows that combining both therapies is safe and opens up a more comprehensive approach to type 2 diabetes management.”
Novo Nordisk’s executive vice president for Development, Martin Holst Lange, emphasized the company’s broader vision: “These results strengthen semaglutide’s profile as a key therapeutic option across the full spectrum of cardiometabolic health, underscoring our continued leadership beyond diabetes and obesity.”
The SOUL trial also reinforced the well-established safety and tolerability of oral semaglutide. No new safety concerns emerged, and the safety profile was consistent with previous trials, supported by more than 33 million patient-years of exposure.
Dr. A. K. Singh, Senior Consultant Endocrinologist at G.D. Hospital & Diabetes Institute in Kolkata, noted, “Oral semaglutide’s dual benefits in glycemic control and cardiovascular protection make it an ideal choice for early intervention in high-risk patients—especially over traditional DPP-4 inhibitors. This marks a significant advancement in holistic diabetes care.”
Following the trial’s success, Novo Nordisk has submitted a label extension application for oral semaglutide to both the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA), with a decision expected in 2025.
Applauding the potential impact of this extension, Dr. V. Mohan, Chairman of Dr. Mohan’s Diabetes Specialities Centre, commented, “Oral semaglutide is now the first and only oral GLP-1 receptor agonist to significantly reduce cardiovascular risk in a high-risk population. This milestone sets a new benchmark in type 2 diabetes treatment, addressing a critical unmet need in cardiometabolic care.”
