Semaglutide Demonstrates Impressive Heart Benefits – Even Before You Lose Weight

Among patients who experienced an early cardiovascular event, those treated with semaglutide had approximately 40% fewer major events at both 3 and 6 months compared to those receiving a placebo, often before most had reached the full target dose.

A new analysis from the landmark SELECT trial reveals that semaglutide can quickly reduce the risk of heart attacks and other serious cardiovascular events in people with overweight or obesity who already have heart disease, even if they do not have diabetes. These results were recently presented at the European Congress on Obesity (ECO) 2025 in Malaga, Spain.

“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 author Dr Jorge Plutzky, Director of Preventive Cardiology, Cardiovascular Medicine at Brigham and Women’s Hospital, Boston, MA, USA and a member of SELECT Steering Committee.

Semaglutide belongs to a class of medications known as GLP-1 receptor agonists. It was originally approved to treat type 2 diabetes, where it already demonstrated heart-protective benefits. It is also approved for weight loss in people with obesity or overweight who have at least one other health condition.

GLP-1 medications mimic the body’s natural incretin hormones. These hormones help regulate blood sugar after meals and signal the brain to reduce hunger. The result is lower calorie intake and support for meaningful weight loss, alongside other potential health benefits.

SELECT Trial’s Groundbreaking Results

In 2023, in a landmark finding, the SELECT trial showed that adults with overweight or obesity but without diabetes, who had previously experienced a heart attack, stroke and/or had peripheral artery disease, taking semaglutide had a 20% reduction in major adverse cardiac events such as heart attacks and strokes compared to those on placebo over the course of 3 years. SELECT was not specifically a weight loss trial; patients received semaglutide or placebo in a blinded manner, but did not receive dietary or weight loss guidance.

This new analysis presented at ECO, focused on the difference in early cardiovascular events with semaglutide versus placebo from randomisation up to 12 months, with a focus on 3 and 6 months, to better understand the drug’s effects, time to cardiovascular benefit, as well as predictors that might help identify patients at risk for early cardiovascular events.

The researchers looked at data from 17,604 adults (aged 45 or older; 72% male) from 804 sites in 41 countries with overweight or obesity (BMI of 27 kg/m² or higher) who were enrolled and treated with weekly injections of semaglutide (at doses slowly titrated to 2.4 mg at week 16) or placebo.

Rapid Risk Reduction Seen in First Months

The study found that semaglutide was associated with a 38% reduced risk of major adverse cardiovascular events (MACE) within the first 3 months compared to placebo (36 vs 58, respectively)

Within the first 6 months, semaglutide was associated with a 41% reduced risk of MACE compared to placebo (67 vs 113, respectively)

Notably, at 3 and 6 months, most patients had not yet lost much weight and many were not yet on the full target dose of semaglutide 2.4 mg weekly.

“Our findings reveal an early separation in the treatment effect of semaglutide that occurs even without a significant amount of weight lost and prior to full semaglutide titration,” said Dr Plutzky. “More research is needed to understand the mechanisms through which semaglutide produces these early clinical benefits, but they may include the drug’s positive effects on reducing inflammation, blood sugar, blood pressure, direct effects on the heart and blood vessels, early dietary changes, or an interaction among these or other responses.”

Despite these important findings, the authors note that SELECT is not a trial looking to prevent first cardiovascular events—all SELECT patients had a history of heart disease, placing them at high risk. It is worth noting, they say, given their cardiovascular history, that SELECT patients were already on other cardio-protective medications, for example, to tackle cholesterol and blood pressure, meaning semaglutide had benefits on top of these other agents.

Meeting: European Congress on Obesity (ECO2025)

The study was funded by Novo Nordisk. JP is an advisor/consultant to Novo Nordisk.

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