What does the SELECT trial prove about semaglutide and heart health?

The SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity, NEJM 2023) enrolled 17,604 adults 45 years and older with established cardiovascular disease, a BMI of 27 or higher, and no diabetes diagnosis. This is the first major cardiovascular outcomes trial with a GLP-1 agonist in a non-diabetic population, and it found that weekly semaglutide 2.4 mg reduced the composite of cardiovascular death, nonfatal heart attack, and nonfatal stroke by 20% compared to placebo over a median of 39.8 months.

The implications of that design are as important as the result. By excluding patients with diabetes, SELECT answered the question that had been implicit in all the earlier trials: is this a diabetic drug that happens to help the heart, or is there something more fundamental happening? The 20% MACE reduction in a non-diabetic, cardiovascular-disease population establishes semaglutide as a cardiovascular risk reduction drug that also produces weight loss, not merely a weight loss drug that is safe in cardiac patients. This reframes the entire conversation about who should be considering this drug. (Lincoff et al., NEJM, 2023)

Cardiologist's calibrated position, Solid (1). A randomized, double-blind, placebo-controlled trial of 17,604 patients is the highest standard of evidence cardiovascular pharmacology offers.

What to do: If you have established cardiovascular disease and a BMI above 27, ask your cardiologist specifically about the SELECT trial. Bring the trial name to the appointment.

For the full picture, read The Drug That Surprised Cardiologists.