Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes
Darren K McGuire1,2, Nikolaus Marx3, Sharon L Mulvagh4
1University of Texas Southwestern Medical Center, Dallas.
The New England Journal of Medicine
|March 31, 2025
Summary
Oral semaglutide significantly reduced major adverse cardiovascular events in patients with type 2 diabetes and atherosclerotic cardiovascular disease or chronic kidney disease. This study confirms cardiovascular benefits without increasing serious adverse events.
Area of Science:
- Cardiology
- Endocrinology
- Nephrology
Background:
- Oral semaglutide, a GLP-1 receptor agonist, has proven cardiovascular safety in type 2 diabetes patients with high cardiovascular risk.
- Further assessment of oral semaglutide's cardiovascular efficacy is needed for patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) or chronic kidney disease (CKD).
Purpose of the Study:
- To evaluate the cardiovascular efficacy of oral semaglutide in individuals with type 2 diabetes and established ASCVD, CKD, or both.
- To assess the safety profile of oral semaglutide in this high-risk population.
Main Methods:
- A double-blind, placebo-controlled, event-driven superiority trial involving 9650 participants aged 50+ with type 2 diabetes and ASCVD/CKD.
- Participants received daily oral semaglutide (up to 14 mg) or placebo, alongside standard care.
- Primary outcome: major adverse cardiovascular events (MACE); secondary outcomes: major kidney disease events.
Main Results:
- Oral semaglutide reduced the risk of MACE by 14% compared to placebo (HR 0.86; 95% CI 0.77-0.96; P=0.006).
- The incidence of MACE was 3.1 events per 100 person-years with oral semaglutide versus 3.7 with placebo.
- No significant difference in major kidney disease events; serious adverse events were similar between groups (47.9% vs 50.3%).
Conclusions:
- Oral semaglutide significantly lowers the risk of major adverse cardiovascular events in patients with type 2 diabetes and ASCVD or CKD.
- The treatment was not associated with an increased incidence of serious adverse events, indicating a favorable safety profile.
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