SELECT: Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity

Background + significance

SELECT was the landmark CVOT establishing GLP-1 cardiovascular benefit in obesity without diabetes — extending the indication beyond T2D for the first time. Led to expanded Wegovy indication for cardiovascular risk reduction in adults with obesity + established CV disease (FDA approved March 2024).

Trial design

Sponsor

Novo Nordisk

Phase

Phase 3

Participants

17,604

Duration

197 weeks

ClinicalTrials.gov ID

NCT03574597

Drugs tested

• Wegovy (semaglutide 2.4 mg)Active

Primary outcome

Time to first major adverse cardiac event (CV death, non-fatal MI, non-fatal stroke) in adults with overweight/obesity + established CV disease but WITHOUT diabetes

20% relative reduction in MACE on semaglutide 2.4 mg vs placebo (HR 0.80, 95% CI 0.72-0.90; P<0.001)

Secondary outcomes

• •Reduction in CV death (HR 0.85)
• •Significant reduction in non-fatal MI (HR 0.72)
• •Mean body-weight reduction 9.4% vs 0.9% placebo
• •Sustained benefit across BMI categories

Why it matters

1. 1.First trial showing GLP-1 CV benefit independent of diabetes.
2. 2.Expanded Wegovy's indication to include cardiovascular risk reduction.
3. 3.Major regulatory + reimbursement implications — Medicare Part D coverage for CV-indication Wegovy followed.