- Question
- Is once-daily oral semaglutide cardiovascularly safe compared with placebo in patients with type 2 diabetes at high cardiovascular risk?
- Design
- Randomized, double-blind, placebo-controlled, event-driven noninferiority trial of 3183 patients. Median time in the trial was 15.9 months.
- Population
- Adults with type 2 diabetes at high cardiovascular risk: age 50 years or older with established cardiovascular disease or chronic kidney disease, or age 60 years or older with cardiovascular risk factors only. Mean age was 66 years.
- Intervention
- Once-daily oral semaglutide added to usual care.
- Control
- Once-daily oral placebo.
- Primary outcome
- Time to first major adverse cardiovascular event (MACE): cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. The noninferiority margin was 1.8 for the upper bound of the 95% CI of the hazard ratio.
- Results
- MACE occurred in 61 of 1591 patients (3.8%) on oral semaglutide and 76 of 1592 (4.8%) on placebo (HR 0.79; 95% CI 0.57 to 1.11; P<0.001 for noninferiority). Cardiovascular death was 0.9% vs 1.9% (HR 0.49; 95% CI 0.27 to 0.92) and all-cause death was 1.4% vs 2.8% (HR 0.51; 95% CI 0.31 to 0.84).
- Safety
- Gastrointestinal adverse events leading to treatment discontinuation were more common with oral semaglutide than with placebo.
- Conclusion
- In patients with type 2 diabetes, the cardiovascular risk profile of oral semaglutide was not inferior to that of placebo.
- Why it matters
- It established the cardiovascular safety of the first oral GLP-1 receptor agonist, and the favorable mortality signals motivated later trials designed to test its cardiovascular benefit.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026