Rybelsus Found to Significantly Reduce Major Adverse Cardiovascular Events in Patients with Type 2 Diabetes, Cardiovascular Disease

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Results from the Phase IIIb SOUL cardiovascular outcomes trial show that Novo Nordisk’s Rybelsus (oral semaglutide) significantly reduced major adverse cardiovascular events (MACE) in adults with type 2 diabetes and cardiovascular disease (CVD) and/or chronic kidney disease (CKD). Full data were presented at the American College of Cardiology's (ACC) Annual Scientific Session and Expo and published in The New England Journal of Medicine.¹

“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,” SOUL steering committee co-chair Darren McGuire, MD, distinguished chair in cardiovascular science, professor of medicine, UT Southwestern, said in a press release. “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 our patients who now have an oral option to improve health outcomes.”

The multicenter, international, randomized, double-blind, parallel-group, placebo-controlled SOUL trial evaluated the effect of Rybelsus in 9,500 patients. The primary endpoint was to demonstrate that the treatment lowers the risk of MACE compared to placebo when both were added to standard of care in patients with type 2 diabetes and established CVD and/or CKD.

Rybelsus met its primary endpoint, reducing the risk of MACE by 14%, including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke compared to placebo. Additionally, a secondary analysis indicated that Rybelsus provided cardiovascular benefits regardless of baseline SGLT2 inhibitor use.

The safety profile of the treatment was consistent with previous semaglutide trials, and no new safety signals were reported. The incidence of serious adverse events (SAEs) was lower in the Rybelsus cohort than in the placebo cohort, primarily due to the higher rate of cardiovascular events and infections in the placebo group. The most common SAEs were cardiac disorders and infections/infestations.

According to Novo Nordisk, cardiometabolic diseases encompass conditions such as cardiovascular and peripheral artery disease, type 2 diabetes, and CKD. When combined, these conditions represent the leading cause of death globally.¹

The World Health Organization (WHO) reports that CVDs account for approximately 17.9 million deaths globally each year, with four out of five fatalities resulting from heart attacks and strokes. In 2019, CVDs were responsible for 32% of all global deaths, with 85% attributed to heart attack and stroke. More than three-quarters of CVD-related deaths occur in low- and middle-income countries.²

The Centers for Disease Control and Prevention (CDC) estimates that in 2021, approximately 38.4 million people in the United States were living with type 2 diabetes, representing 11.6% of the population. Prevalence increases with age, affecting 29.2% of individuals over 65 years old.³

According to the Centers for Disease Control and Prevention, approximately 38.4 million people in the United States were living with type 2 diabetes in 2021, representing 11.6% of the population. It was more common with age, as 29.2% of people over 65 years of age were living with the condition.⁴

“Novo Nordisk continues to evolve its focus beyond diabetes and obesity towards a broader spectrum of metabolic and cardiovascular health,” said Martin Holst Lange, EVP, development, Novo Nordisk, in the press release. “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.”

References

1. Novo Nordisk A/S: Rybelsus® (oral semaglutide 14 mg) demonstrates superior reduction in cardiovascular events in the SOUL trial at ACC 2025. Novo Nordisk. March 29, 2025. Accessed April 1, 2025. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=915967

2. Cardiovascular diseases. WHO. Accessed April 1, 2025. https://www.who.int/health-topics/cardiovascular-diseases#tab=tab_1

3. Cardiovascular diseases (CVDs). WHO. June 11, 2021. Accessed April 1, 2025. https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)#:~:text=Key%20facts,38%25%20were%20caused%20by%20CVDs.

4. National Diabetes Statistics Report. CDC. Accessed April 1, 2025. https://www.cdc.gov/diabetes/php/data-research/index.html