Oral Semaglutide Reduces MACE Risk in People With Type 2 Diabetes and CVD

Oral semaglutide has demonstrated a statistically significant and superior reduction in major adverse cardiovascular events (MACE) of 14% compared with placebo in adults with type 2 diabetes (T2D), according to new data from the SOUL trial.¹

"We are pleased to see that the results from SOUL demonstrate that oral semaglutide reduces the risk of cardiovascular events and that the benefits of oral semaglutide come on top of standard of care,” Martin Holst Lange, executive vice president and head of Development at Novo Nordisk said in a statement.¹ “Approximately 1 in 3 adults with T2D also have cardiovascular disease; therefore, it is crucial to have therapies that can address both conditions.”

With these new findings, the SOUL trial, which enrolled 9,650 people with T2D and established cardiovascular disease (CVD) and/or chronic kidney disease (CKD), has met its primary endpoint. The trial was an international, randomized, multicenter, double-blind, placebo-controlled phase 3 trial. As part of standard of care, 49% of patients received SGLT2i at some point during the trial. Oral semaglutide continued to have a safe and well-tolerated profile in line with previous findings.¹

The FDA originally approved oral semaglutide, which is marketed under the name Rybelsus, in September 2019 for treating adults with T2D.2 In 2023, the FDA approved a label update for oral semaglutide allowing it to be used in first-line treatment of patients with T2D.³

Following data from SOUL, Novo Nordisk plans to file for regulatory approval of a label expansion for oral semaglutide as a therapy indicated for reducing MACE risk in adults with T2D and established CVD in both the United States and European Union. Detailed results from SOUL will be presented at a scientific conference in 2025.¹

While Rybelsus is the oral formulation of semaglutide, the therapy has made headlines in recent years for off-label use for weight loss in its injectable formuations, namely, Ozempic. Novo Nordisk also recently presented data on injectable semaglutide in patients with T2D and CKD in March 2024, which found that injectable semaglutide 1.0 mg was associated with a 24% reduction in risk of kidney disease-related events in topline results of the FLOW trial.⁴

"Ozempic has demonstrated A1c reduction, cardiovascular risk reduction and, now, top-line FLOW results of 24% reduction in the risk of kidney disease-related events in people with type 2 diabetes and chronic kidney disease compared to placebo. This adds significantly to the options for treatments for the 40% of patients that develop diabetes-related CKD," said HCPLive advisory board member Natalie Bellini, DNP, program director of Diabetes Technology at University Hospitals Diabetes and Metabolic Care Center.⁴ "Clinically I cannot wait to see what combination therapy with SGLT2 inhibitors and/or Kerendia will demonstrate."

REFERENCES

1. Novo Nordisk A/S: Oral semaglutide demonstrates a 14% reduction in risk of major adverse cardiovascular events in adults with type 2 diabetes in the SOUL trial. News release. Novo Nordisk. October 21, 2024. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=171480

2. Kunzmann K. FDA Approves Oral Semaglutide for Patients with Type 2 Diabetes. News article. September 20, 2019. https://www.hcplive.com/view/fda-semaglutide-type-2-diabetes

3. Campbell P. FDA Updates Label for Oral Semaglutide, Making Agent a First-Line Therapy in Type 2 Diabetes. News article. January 13, 2023. https://www.hcplive.com/view/fda-updates-label-for-rybelsus-oral-semaglutide-first-line-therapy-in-type-2-diabetes

4. Novo Nordisk. Novo Nordisk A/S: Semaglutide 1.0 mg demonstrates 24% reduction in the risk of kidney disease-related events in people with type 2 diabetes and chronic kidney disease in the FLOW trial. Novo Nordisk Press Releases. March 5, 2024. Accessed March 5, 2024. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=167028#.