- Question
- Is once-weekly semaglutide cardiovascularly safe in patients with type 2 diabetes, and can it reduce cardiovascular events?
- Design
- Randomized, double-blind, placebo-controlled, multinational, multicenter phase 3 trial of 3297 patients with 104 weeks of treatment. The main hypothesis was noninferiority, with a margin of 1.8 for the upper boundary of the 95% CI of the hazard ratio.
- Population
- Adults with type 2 diabetes on standard care at high cardiovascular risk; 2735 patients (83.0%) had established cardiovascular disease, chronic kidney disease, or both.
- Intervention
- Once-weekly semaglutide, 0.5 mg or 1.0 mg, added to standard care.
- Control
- Once-weekly placebo (with matching doses), added to standard care.
- Primary outcome
- First occurrence of the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
- Results
- The primary outcome occurred in 108 of 1648 patients (6.6%) with semaglutide and in 146 of 1649 (8.9%) with placebo (HR 0.74; 95% CI 0.58 to 0.95; P<0.001 for noninferiority). Nonfatal stroke was less frequent with semaglutide (1.6% vs 2.7%; HR 0.61; 95% CI 0.38 to 0.99; P=0.04), whereas nonfatal myocardial infarction did not differ significantly (2.9% vs 3.9%; HR 0.74; 95% CI 0.51 to 1.08; P=0.12).
- Safety
- Fewer serious adverse events occurred with semaglutide, but more patients discontinued treatment because of adverse events, mainly gastrointestinal. Retinopathy complications were more frequent with semaglutide (HR 1.76; 95% CI 1.11 to 2.78; P=0.02), while new or worsening nephropathy was less frequent.
- Conclusion
- In patients with type 2 diabetes at high cardiovascular risk, semaglutide significantly reduced the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke compared with placebo, confirming noninferiority.
- Why it matters
- It provided evidence that a once-weekly GLP-1 receptor agonist is not only cardiovascularly safe but may lower events in high-risk people with type 2 diabetes, and highlighted the need to monitor retinopathy.
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