Oral Semaglutide Reduced MACE Risk in T2D with CVD, CKD

Used as an adjunct to standard of care, oral semaglutide is associated with a statistically significant reduction in major adverse cardiovascular events (MACE) in individuals with type 2 diabetes (T2D) and cardiovascular disease and/or chronic kidney disease, announced Novo Nordisk in a news release.¹

Results of the SOUL clinical trial will be presented at a scientific meeting in 2025. | Image credit: mihail - stock.adobe.com

In the double-blind, randomized, multicenter, phase 3 SOUL trial (NCT03914326), a cohort of 9650 participants (71.1% men, 68.9% white, mean age, 66.1 years) were randomly assigned 1:1 to receive either oral semaglutide or placebo therapy. Primary outcomes included time to first occurrence of MACE, including cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.²

Confirmatory secondary outcomes included time to first occurrence of a composite outcome of cardiovascular death, kidney-related death, persistent 50% or more reduction in estimated glomerular filtration rate (eGFR), persistent eGFR less than 15 mL/min/1.73m2, or initiation of dialysis or kidney transplant, as well as time to occurrence of cardiovascular death and time to first occurrence of major adverse limb events, including acute or chronic limb ischemia hospitalization.

Per the news release,¹ the SOUL trial achieved its primary endpoint, with oral semaglutide demonstrating “a statistically significant and superior reduction in MACE” of 14% compared with the placebo group. All 3 primary endpoint components “contributed to the superior MACE reduction demonstrated by oral semaglutide.”

Additionally, oral semaglutide demonstrated a safe and well-tolerated safety profile, similar to previous trials of the drug.

READ MORE: SGLT2i, GLP-1RA Combination Therapy Offers Robust Protection Against Cardiovascular, Kidney Disease

"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,” said Martin Holst Lange, executive vice president and head of development at Novo Nordisk. “Approximately one in three adults with type 2 diabetes also have cardiovascular disease; therefore, it is crucial to have therapies that can address both conditions.”

The company anticipates filing for regulatory approval of a label expansion for oral semaglutide (Rybelsus) in early 2025. Additionally, detailed results of the SOUL clinical trial will be presented at a scientific meeting in 2025.

Oral semaglutide is indicated for use in adults with insufficiently controlled T2D as a therapy to improve glycemic control adjunct to diet and exercise. It is available in 3 mg, 7 mg, and 14 mg doses.

READ MORE: Diabetes Resource Center

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. Accessed October 22, 2024. https://novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id=171480

2. McGuire DK, Busui RP, Deanfield J, et al Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial. Diabetes Obes Metab. 2023;25(7):1932-1941. doi:10.1111/dom.15058