SELECT — Semaglutide in Obesity Without Diabetes

Design

SELECT (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) randomised 17,604 adults aged ≥45 with BMI ≥27 and established cardiovascular disease but no diabetes to weekly semaglutide 2.4 mg subcutaneous or placebo, mean follow-up ~40 months.

Findings

• Primary composite (CV death, non-fatal MI, non-fatal stroke): 20% relative reduction (HR 0.80, p<0.001).
• Components individually: meaningful reductions in MI; weaker for stroke.
• Heart-failure hospitalisation: reduced.
• Weight loss: ~9.4% sustained vs. 0.9% in placebo.
• All-cause mortality: trend toward reduction.
• Adverse events: gastrointestinal as expected; gallbladder disease modestly increased.

Why it matters

SELECT is the first major RCT to show cardiovascular event reduction in non-diabetic obese adults from a GLP-1 agonist. It moves obesity firmly into the cardiometabolic-disease category that deserves pharmacological treatment beyond lifestyle alone, and supports broader GLP-1 use in primary prevention.

Open questions

• Are the benefits primarily mediated by weight loss, or by independent cardiovascular pharmacology?
• How does benefit translate to lower-risk obese adults without prior cardiovascular disease?
• What is the long-term safety profile beyond 4–5 years?
• Does the cardiovascular benefit persist after stopping the drug?

Related entries

GLP-1 agonists, Cardiovascular disease, Type 2 diabetes.