Beyond the Scale: The SELECT Trial and Heart Health

Most GLP-1 coverage is about the scale. One large trial asked a different question: does the medication change what happens to the heart? This guide explains what the SELECT trial found, who it studied and what it cannot tell us. It is general education, not medical advice, and it does not suggest any product, dose or provider.

Who was studied

SELECT enrolled 17,604 adults aged 45 and older who had overweight or obesity and already had cardiovascular disease, such as a previous heart attack, stroke or peripheral artery disease. None of them had diabetes. They were randomly assigned to receive semaglutide or a placebo, on top of usual care, and were followed for an average of about 40 months (39.8 months).

What the trial measured

The main outcome was a combination of three events: death from cardiovascular causes, a nonfatal heart attack or a nonfatal stroke. Researchers counted how many people in each group had at least one of them.

The results

• Semaglutide group: 569 of 8,803 people (6.5%) had one of those events.
• Placebo group: 701 of 8,801 people (8.0%) had one.
• The difference: a relative reduction of about 20 percent, or roughly 1.5 percentage points in absolute terms over the follow-up period.

Weight and waist size also fell more in the semaglutide group. After about four years, the average change was roughly 10 percent of body weight, compared with about 1.5 percent in the placebo group.

How to read those numbers

A 20 percent relative reduction sounds large, and for people at high risk it matters. It helps to hold the absolute numbers next to it: most people in both groups did not have one of these events during the trial. The benefit is a shift in odds, not a guarantee for any one person.

What the trial cannot tell us

• It studied people who already had heart disease. The results do not automatically apply to people with overweight or obesity who have never had a heart event.
• Side effects were part of the picture. More people in the semaglutide group stopped treatment than in the placebo group, mostly because of stomach-related symptoms. Our guide to side effects in the big GLP-1 trials goes through them.
• The trial was funded by the drug’s manufacturer. That is common for large drug trials and does not by itself make a result wrong, but it is worth knowing when you read headlines.
• Three and a half years is not a lifetime. What happens after people stop is a separate question; see what happens when you stop a GLP-1 medication.

What this means in practice

If you or someone you care about has heart disease and is wondering whether a medication like this is relevant, the right next step is a conversation with the clinician who knows your history. Trial results describe groups. A prescriber weighs them against your own risks, other medications and goals.

To sum up

SELECT is one of the stronger pieces of evidence that a GLP-1 medication can lower the chance of a heart attack, stroke or cardiovascular death in people with existing heart disease and excess weight, and it is a reminder that these drugs are studied for more than weight alone. It does not make them right for everyone, and it does not replace the basics of heart health.

Sources

• Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). New England Journal of Medicine, 2023.
• Lingvay I, et al. Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nature Medicine, 2024.
• American College of Cardiology, summary of the SELECT trial presented at the American Heart Association Scientific Sessions, November 2023.
• Cleveland Clinic Newsroom, “International clinical trial finds that semaglutide reduced cardiovascular events by 20% in adults with overweight or obesity who don’t have diabetes,” November 2023.