Early cardiovascular benefits of semaglutide seen within months in SELECT trial

Semaglutide can rapidly reduce heart attacks and other serious cardiovascular complications in adults with overweight or obesity who have pre-existing cardiovascular disease but not diabetes, according to a secondary analysis of the landmark Semaglutide and Cardiovascular Outcomes (SELECT) trial from the same international author team being presented at this year's European Congress on Obesity (ECO) in Malaga, Spain (11-14 May).

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." 

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

Semaglutide is a GLP-1 medication initially approved for treating adults with type 2 diabetes, in whom it has already shown cardiovascular benefit. But semaglutide is also approved for weight loss in people with obesity or overweight who have at least one other health issue.

This GLP-1 class of medications simulate the functions of the body's natural incretin hormones, which help to lower blood sugar levels after a meal and provide a fullness signal to the brain, helping patients to lower daily calorie intake and promoting their weight loss.

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 [1]. 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.

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.