Research indicates that the weight-loss medication Wegovy can lower the risk of heart attacks and other cardiovascular conditions, even in individuals who may not experience significant weight loss or those who aren’t severely obese.

Earlier findings from the SELECT trial hinted that Wegovy, a GLP-1 weight-loss drug, could have these heart health benefits, but it remained unclear if they were solely due to weight reduction. Studies involving pigs suggested a direct protective effect on the heart, now validated in humans.

“The important takeaway is that the cardiovascular advantages of these drugs occur independently of weight loss. This repositions them as drugs that modify diseases rather than merely aiding weight loss,” explains John Deanfield from University College London.

Wegovy contains semaglutide, a GLP-1 treatment, as well as Ozempic, which is designed for managing type 2 diabetes. While these treatments are approved for weight management and diabetes, they have shown promise in various other conditions, including dementia and alcoholism.

The SELECT trial assessed semaglutide against placebo regarding cardiovascular risks in 17,604 participants aged 45 and older who were overweight or obese. None were diabetic, yet all had some heart disease. In November 2023, Deanfield et al. announced that semaglutide reduced the likelihood of heart attacks, strokes, and other severe cardiac events by 20%.

Researchers are analyzing data to determine if these effects are solely due to weight loss, examining various body mass index (BMI) and weight loss ranges. They discovered that individuals starting with a BMI of 27—categorized as mildly obese—showed improved heart disease risk after using semaglutide, as did the severely obese with a BMI of 44.

Interestingly, the degree of weight lost seemed to have minimal impact on cardiovascular improvements, whether during the initial 20 weeks or throughout the nearly two-year study.

However, abdominal fat appears to play a significant role. Researchers noted that a slimmer waist at the study’s onset correlated with reduced heart disease risk, regardless of whether participants received semaglutide or a placebo. Moreover, after years on semaglutide, each 5-centimeter reduction in waist size was linked to a 9% decrease in cardiovascular event risk. The research team found that waistline reduction contributed to nearly one-third of the drug’s heart-protective effects, while the reasons for the other benefits remain unclear.

These results reinforce semaglutide’s potential beyond just weight management, as individuals in the placebo group even experienced a slight rise in heart disease risk while losing weight; this may be reflective of an underlying health issue, Deanfield notes.

Further studies are required to unpack how semaglutide and potentially other GLP-1 medications exert these benefits. Professor Deanfield speculates that enhancements in blood vessel function and blood pressure could be at play, alongside possible anti-inflammatory effects.

“Inflammation is a crucial mechanism influencing various diseases we want to avoid,” he mentions. “This appears to be a shared pathway targeted by these drugs.”

This advantage might also be linked to how semaglutide interacts with fat surrounding the heart, referred to as epicardial adipose tissue. Gianluca Iacobellis from the University of Miami highlights, “Semaglutide binds to epicardial adipose tissue receptors to enhance tissue health, consequently improving heart function and lowering cardiovascular event risks.”

“The query remains: What criteria should we establish to identify individuals most likely to benefit from these drugs?” questions Stefano Masi from the University of Pisa, Italy. “This is an ongoing challenge.”