Wegovy May Protect the Heart Sooner Than Expected

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A new analysis of the SELECT trial shows that semaglutide (Wegovy), a medication commonly used for weight loss and diabetes, may reduce the risk of heart attacks, strokes and other major heart problems in people with obesity and existing heart disease — even before they lose much weight.

“These results highlight semaglutide’s early action on decreasing major cardiovascular events, with significant benefits already evident by the first 6 months, and for some, even earlier, even before any major weight loss and before most patients would have been titrated to their full target dose of 2.4 mg,” said lead investigator Jorge Plutzky, M.D., director of Preventive Cardiology, Cardiovascular Medicine at Brigham and Women’s Hospital and a member of SELECT Steering Committee.

Semaglutide is part of a class of medications called GLP-1 receptor agonists. These drugs work by mimicking natural hormones that control blood sugar and help people feel full after eating, which can lead to weight loss. It was originally approved for people with Type 2 diabetes but is now also used for weight management in people with obesity or overweight who have at least one other health problem.

In 2023, the SELECT trial showed that semaglutide reduced the risk of major heart events (such as heart attacks and strokes) by 20% over three years in adults with obesity who had a history of heart disease but not diabetes. Importantly, this study did not include weight loss counseling, so the benefits came from the drug alone.

Now, investigators have taken a closer look at how quickly those heart benefits appear. This new analysis, presented at the European Congress on Obesity, examined early cardiovascular events in 17,604 patients aged 45 years or older from 41 countries. All participants had a body mass index (BMI) of 27 or higher and a history of heart disease. They were randomly given semaglutide (starting at low doses and gradually increasing to 2.4 mg weekly) or a placebo.

Here’s what the new data showed:

• Within the first three months, people taking semaglutide had a 38% lower risk of major heart problems compared with those on placebo.
• By 6 months, the risk was 41% lower than placebo.

Most people had not lost significant weight or reached the full semaglutide dose by this time — suggesting that semaglutide provides heart protection early on, even before weight loss begins.

This is especially important for people who have already had heart issues and are at high risk of future events. Patients in the SELECT trial were also taking other cardioprotective medications, such as those to control blood pressure and cholesterol, meaning semaglutide provided benefits on top of standard treatments.

While this study did not look at whether semaglutide can prevent heart disease in people without existing conditions, it highlights how quickly the drug can help protect people with a history of heart problems.

Plutzky said that although more research is necessary to understand how the drug produces these early benefits, he believes it may have to do with reductions in blood sugar, blood pressure, inflammation or early dietary changes, among others.

“For people with obesity and existing cardiovascular disease, preventing another heart attack or stroke is vitally important,” noted Jason Brett, M.D., principal medical head at Novo Nordisk Inc. “Seeing this SELECT secondary data demonstrate that patients experienced major adverse cardiovascular events (MACE) risk reduction within three months is remarkable.”