Novo Nordisk reports SOUL trial results showing reduced cardiovascular risk with oral semaglutide in type 2 diabetes
Phase 3b trial data presented at ACC and published in NEJM highlights cardiovascular outcomes of oral semaglutide in patients with type 2 diabetes and coexisting chronic conditions
Novo Nordisk has released full results from the SOUL cardiovascular outcomes trial, a phase 3b study evaluating the impact of oral semaglutide on adults with type 2 diabetes who also have cardiovascular disease (CVD) and/or chronic kidney disease (CKD). The findings were presented during a late-breaking clinical session at the American College of Cardiology’s Annual Scientific Session and Expo in Chicago and were simultaneously published in the New England Journal of Medicine.
The SOUL trial met its primary endpoint by demonstrating a 14 per cent reduction in the risk of major adverse cardiovascular events (MACE) when treated with oral semaglutide versus placebo. Each component of MACE contributed to the outcome, including a 26 per cent reduction in nonfatal myocardial infarction, 12 per cent in nonfatal stroke, and 7 per cent in cardiovascular death. Notably, participants from the Asian region showed a 27 per cent reduction in MACE risk.
Dr A.G. Unnikrishnan, CEO and Chief of Endocrinology at the Chellaram Diabetes Institute, Pune, noted, “In an important news from the SOUL trial, oral semaglutide has shown it can reduce the risk of major adverse cardiovascular events (MACE), regardless of whether participants were already using sodium-glucose cotransporter-2 inhibitor (SGLT2i). The benefits were consistent for everyone—those on SGLT2i and those without—during the trial. What is even better is that combining these two treatments was a safe approach, opening the door to a more comprehensive, all-rounded approach to managing type 2 diabetes. This breakthrough not only transforms care for people living with type 2 diabetes but also sets a new standard for management of type 2 diabetes and cardiovascular management.”
Cardiometabolic conditions, including CVD, type 2 diabetes, peripheral artery disease, and CKD, are collectively a major cause of global mortality.
Martin Holst Lange, executive vice president for Development at Novo Nordisk, stated, “Novo Nordisk continues to evolve its focus beyond diabetes and obesity towards a broader spectrum of metabolic and cardiovascular health. These data, alongside our other data being presented at ACC, reinforce the comprehensive set of health benefits of semaglutide, making it a strong option for healthcare professionals addressing the spectrum of metabolic and cardiovascular health – and our continued leadership in the space.”
The overall safety profile of oral semaglutide in the SOUL trial was aligned with previous semaglutide studies. No new safety signals were identified. The data support the established safety and tolerability of semaglutide, which now includes over 33 million patient years of usage.
Dr A.K. Singh, Senior Consultant Endocrinologist at G.D. Hospital & Diabetes Institute, Kolkata, and adjunct Professor at Institute of Medical Science & SUM Hospital, Bhubaneswar, stated, “The SOUL trial confirms that oral semaglutide significantly reduces cardiovascular risk in type 2 diabetes (T2D). This makes it a key oral antidiabetic drug (OAD) for early intervention, especially for high CV risk patients ahead of a DPP-4 inhibitor. Its cardio-metabolic benefits offer a holistic approach to T2D management, improving both blood sugar and cardiovascular health. Oral semaglutide represents a major advance in diabetes care, prioritising both glycemic control and heart protection.”
Based on the SOUL trial data, Novo Nordisk has submitted a label extension application for oral semaglutide. The application has been accepted for review by both the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), with decisions expected in 2025.
Dr V. Mohan, Chairman of Dr. Mohan’s Diabetes Specialities Centre, commented, “This data reinforces oral semaglutide’s groundbreaking role as the first and only approved oral glucagon-like peptide-1 receptor agonist (GLP-1 RA) to achieve a significant reduction in cardiovascular risk within this high-risk population. This achievement enhances the existing standards of care for managing both T2DM and CVD, offering patients an innovative and effective therapeutic intervention. The observed impact of oral semaglutide on cardiovascular outcomes underscore its potential to address a critical unmet need in type 2 diabetes and cardiometabolic disease management.”