’Weight loss’ drug semaglutide linked to better heart health

The weight loss drug semaglutide delivers cardiovascular benefits irrespective of starting weight and amount of weight lost, according to preliminary findings from a UCL-led research team.

The findings, presented at this year’s European Congress on Obesity (ECO), suggest that even people with mild obesity or those not losing weight are likely to gain some cardiovascular advantage.

Led by Professor John Deanfield (UCL Institute of Cardiovascular Disease), the study looked at data from the landmark Semaglutide and Cardiovascular Outcomes (SELECT) trial - the largest and longest clinical trial of the effects of semaglutide on weight in over 17,000 adults with overweight and obesity but not diabetes, run by an international team involving Professor Deanfield.

The analysis, which is not yet published, examined the relationship between weight measures at baseline, and change in weight during the study, with cardiovascular outcomes. These included time to first major adverse cardiovascular event and heart failure measures.

Professor Deanfield said: "These findings have important clinical implications. 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.

"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.

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

Semaglutide is a GLP-1 medication 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 simulates the functions of the body’s natural incretin hormones, which helps to lower blood sugar levels after a meal. Adjusting these hormone levels can also make people feel full, and in doing so, helps lower their daily calorie intake.

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

Between October 2018 and June 2023, 17,604 adults (aged 45 or older; 72% male) from 804 sites in 41 countries with overweight or obesity (BMI of 27 kg/m or higher) were enrolled and treated with semaglutide (2.4mg) or placebo for an average of 40 months. They had previously experienced a heart attack, stroke and/or had peripheral artery disease, but did not have type 1 or type 2 diabetes when they joined the study.

The authors caution that SELECT is not a primary prevention trial so that the data cannot be extrapolated to all’adults with overweight and obesity to prevent major adverse cardiovascular events; and despite being large and diverse, it does not include enough individuals from different racial groups to understand different potential effects.

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

The lead author of that study, Professor Donna Ryan from Pennington Biomedical Research Center, New Orleans, USA, said: "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."

    Mark Greaves

    m.greaves [at] ucl.ac.uk

    +44 (0)20 3108 9485
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