People taking the drug semaglutide not only lost around 10% of their body weight but had cardiovascular benefits irrespective of their starting weight or the amount of weight lost, according to research.
New data from the largest and longest clinical trial on the effects of semaglutide on weight loss, found the effects lasted for four years, and the heart benefits could have occurred through some other mechanism unrelated to weight loss.
A study, led by Professor Donna Ryan from Pennington Biomedical Research Centre in New Orleans, published in Nature Medicine, examined the long-term weight effects of semaglutide; while another led by Professor John Deanfield from University College London investigated whether the cardiovascular benefits were related to starting weight or the amount of weight lost.
“Clinically meaningful weight loss was achieved by men and women of all races, ages, and body sizes, across all regions, with a lower rate of serious adverse events compared with placebo,” Professor Ryan said.
“Over half of adults taking semaglutide moved down at least one BMI category after 2 years compared to 16%receiving placebo; and 12% reached a healthy BMI (25 kg/m² or less) compared with 1% in the placebo group.”
“Importantly, the findings also indicate that semaglutide delivers cardiovascular benefits irrespective of starting weight and the amount of weight lost—suggesting that even patients with mild obesity or those not losing weight are likely to gain some advantage,” Professor Deanfield said.
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/m² or higher) were enrolled in the SELECT trial and treated with semaglutide (2.4mg) or placebo for an average of 40 months.
The participants 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.
By the end of the trial, scientists 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.
In the semaglutide group, weight loss continued to week 65 and was sustained for four years, with participants’ losing on average 10.2% of their body weight and 7.7cm from their waistline, compared with 1.5% and 1.3cm respectively in the placebo group.
These improvements were seen across both sexes and all categories of race and age, irrespective of starting blood sugar (glycaemic) status or metabolically unhealthy body fat, yet women taking semaglutide tended to lose more weight on average than men.
A third study on the side effects of the drug found that there were no unexpected safety issues with semaglutide and surprisingly, the proportion of participants with serious adverse events was lower in the semaglutide group than the placebo group (33% vs 36%), mainly driven by differences in cardiac disorders.
However, more patients on semaglutide discontinued the trial due to gastrointestinal symptoms, including nausea and diarrhoea, during the 20-week dose escalation phase, and while semaglutide did not lead to an increased rate of pancreatitis, rates of cholelithiasis (gallbladder stones) were higher in this group.
“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,” Professor Deanfield said.
“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.”
Despite these important findings, the authors cautioned that SELECT was not a primary prevention trial so the data could not be extrapolated to prevent MACE in all adults with obesity.