The SELECT trial, published in the New England Journal of Medicine in November 2023, found that semaglutide — the GLP-1 drug already approved for diabetes and obesity — reduced major cardiovascular events by 20 percent relative to placebo in 17,604 adults with established cardiovascular disease and overweight or obesity but without diabetes, over a median follow-up of about three years. Roughly 6.5 percent of the semaglutide group and 8.0 percent of the placebo group experienced the composite endpoint of cardiovascular death, nonfatal heart attack, or nonfatal stroke. Engevity News covers the finding with its design and its limits; this is information, not medical advice, and readers with health questions should talk to their own clinician.
The result matters because it was the first trial of its size to show cardiovascular benefit from an obesity medication in people without diabetes — moving the drug class from body-weight medicine to cardiovascular medicine.
What did the trial actually do?
The four required elements, from the published paper. What was found: a 20 percent relative reduction in the three-part composite endpoint, a result that cleared the statistical bar. In whom: adults 45 and older with prior cardiovascular disease and a body-mass index of 27 or greater, none with diabetes — a population distinct from the diabetes trials that built the drug's cardiovascular evidence base. How big: the absolute difference was about 1.5 percentage points over roughly three years, which is the number clinicians weigh against the drug's cost and side effects, and the trial also documented a mean weight loss near 10 percent in the treatment arm. What it could not show: the trial was not designed to test individual endpoint components separately with the same confidence, and its population — established heart disease — excludes the people now taking the drug for weight alone.
How do we know this?
The design, per the paper and the trial's registered entry at ClinicalTrials.gov: a randomized, double-blind, placebo-controlled trial across 41 countries, with participants assigned to weekly injected semaglutide or placebo on top of standard preventive care, followed for a planned span extended to accumulate enough events. Randomized, placebo-controlled enrollment at this scale is the strongest single-study design medicine has; the double-blinding keeps expectation effects out. The trial's manufacturer funded it — a disclosed conflict the paper states plainly, and one reason the independent cardiology community's response, including commentary in specialist journals, treated replication and longer follow-up as the open items.
What has happened since?
Regulators moved: in March 2024 the US Food and Drug Administration approved semaglutide for reducing cardiovascular risk in adults with established disease and overweight or obesity, per the agency's approval notice — an indication that took the drug out of the weight-loss aisle and into cardiovascular prevention. Subsequent trials have since reported kidney and heart-failure benefits in other populations, per their published results, each with its own design and limits. What the SELECT record establishes is one well-designed trial's answer in one population. What it does not establish is benefit for the broader population now taking the drug — that question, as the trial's own authors note, is a different trial.
For more context, read How do scientists know how old a fossil is?.