Weight loss drug could reduce the risk of heart attacks and strokes, study finds

At this year’s European Congress on Obesity (ECO), researchers unveiled promising findings regarding the cardiovascular benefits of semaglutide, even for individuals with mild obesity or those not losing significant weight.

The study, led by Professor John Deanfield of the UCL Institute of Cardiovascular Disease, analyzed data from the Semaglutide and Cardiovascular Outcomes (SELECT) trial, the largest and longest clinical trial examining the effects of semaglutide on weight in over 17,000 adults with overweight and obesity but not diabetes.

The SELECT trial, conducted by an international team, including Professor Deanfield, enrolled 17,604 adults aged 45 or older from 804 sites in 41 countries. Participants had a body mass index (BMI) of 27 kg/m² or higher and had previously experienced a heart attack, stroke, or peripheral artery disease but did not have type 1 or type 2 diabetes. They were treated with either 2.4 mg of semaglutide or a placebo for an average of 40 months between October 2018 and June 2023.

The primary focus of the study was to assess the relationship between baseline weight measures, weight change during the study, and cardiovascular outcomes, including the time to the first major adverse cardiovascular event and heart failure measures.

Professor Deanfield emphasized the significant clinical implications of these findings: “Around half of the patients that I see in my cardiovascular practice have levels of weight equivalent to those in the SELECT trial and are likely to derive benefit from taking semaglutide on top of their usual level of guideline-directed care."

The analysis revealed that the cardiovascular benefits of semaglutide were independent of the amount of weight lost.

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“Our findings show that the magnitude of this treatment effect with semaglutide is independent of the amount of weight lost, suggesting that the drug has other actions which lower cardiovascular risk beyond reducing unhealthy body fat,” Deanfield explained.

These alternative mechanisms may include positive impacts on blood sugar, blood pressure, inflammation, and direct effects on the heart muscle and blood vessels, or a combination of these factors.

Semaglutide, a GLP-1 medication, is primarily prescribed for adults with type 2 diabetes but is also approved for weight loss in people with obesity or overweight who have at least one other health issue. This class of medications mimics the functions of the body’s natural incretin hormones, which help lower blood sugar levels after a meal. By adjusting these hormone levels, semaglutide can also induce a feeling of fullness, helping individuals lower their daily calorie intake.

In 2023, the SELECT trial reported that adults with overweight or obesity but not diabetes who took semaglutide for more than three years had a 20% lower risk of heart attack, stroke, or death due to cardiovascular disease. Additionally, they lost an average of 9.4% of their body weight.

Despite the promising results, the authors caution that SELECT is not a primary prevention trial, meaning the data cannot be extrapolated to all adults with overweight and obesity to prevent major adverse cardiovascular events. Furthermore, while the trial was large and diverse, it did not include enough individuals from different racial groups to fully understand the potential effects across various populations.

A separate study, co-authored by Professor Deanfield and published in Nature Medicine, also analyzed SELECT trial data and found that semaglutide achieved clinically meaningful weight loss over at least four years in men and women of all races, ages, and body sizes, with a lower rate of serious adverse events compared to placebo.

Professor Donna Ryan from Pennington Biomedical Research Center, the lead author of this study, highlighted the potential public health impact: “Our long-term analysis of semaglutide establishes that clinically relevant weight loss can be sustained for up to four years in a geographically and racially diverse population of adults with overweight and obesity but not diabetes. This degree of weight loss in such a large and diverse population suggests that it may be possible to impact the public health burden of multiple obesity-related illnesses. While our trial focused on cardiovascular events, many other chronic diseases including several types of cancer, osteoarthritis, and anxiety and depression would benefit from effective weight management.”

These results open new avenues for managing cardiovascular risk in this population, emphasizing the need for further research to explore the drug's full potential and its impact on various health outcomes.

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