Two important studies were presented at this year’s European Congress on Obesity (ECO), based on the landmark Semaglutide and Cardiovascular Outcomes (SELECT) trial from the same international author group.
Led by Professor John Deanfield from University College London, one study examined the relationship between weight measures at baseline and change in weight during the study with cardiovascular outcomes.
The other study, led by Professor Donna Ryan from Pennington Biomedical Research Centre, New Orleans, examined the long-term weight effects of semaglutide.
Deanfield said the anti-obesity injections reduced the CVD risk in obese people regardless of the amount of weight they lost while on the drug, and that the findings suggest the treatment could have effects beyond reducing unhealthy body fat.
He hailed the drugs as having a “potentially very important place in treatment”, with “wide-scale opportunity”, reports The Independent.
The five-year study comprised 17 604 adults from 45 from 41 countries and examined the amount of time before patients suffered major cardiovascular events.
After 20 weeks on semaglutide, 62% of patients had lost more than 5% of their bodyweight compared with 10% in the placebo group, with the risk reduction of heart attacks, stroke or heart failure similar in patients regardless of whether they lost weight or not.
In August, researchers found semaglutide reduced the risk of a heart attack or stroke in obese people with cardiovascular disease by a fifth. A 2.4mg once-weekly dose of Wegovy, alongside standard care for the prevention of heart attacks or stroke, lowered the risk by 20% compared with those given a placebo.
Speaking at the ECO this week, where he presented the findings, Deanfield called the trial a game-changer.
“In the 1990s, when statins came in, we figured out there was a class of drugs that would change the biology of this disease. That was a major breakthrough to transform cardiology practice. We now have a class of drugs that could equally transform many chronic diseases of ageing.
“Our findings show… the drug has other actions that 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.”
Sustained weight loss
On a second piece of research based on the SELECT trial, presented at the ECO and led by Ryan, she said weight loss using semaglutide can be sustained for up to four years in overweight or obese adults who do not have diabetes.
Patients on semaglutide lost an average 10.2% of their body weight and 7.7cm from their waistline, compared with 1.5% and 1.3cm respectively in the group on a placebo.
After two years, 52% of people treated with semaglutide had moved down to a lower BMI category compared with 16% in the placebo group.
The findings were published in Nature Medicine.
“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,” said Ryan.
Despite these important findings, 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 MACE (major adverse cardiovascular event); and despite being large and diverse, it does not include enough individuals from different racial groups to understand different potential effects.
Study details
Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial
Donna Ryan, Ildiko Lingvay, John Deanfield, Robert Kushner et al.
Published in Nature on 13 May 2024
Abstract
In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with pre-existing cardiovascular disease, overweight or obesity, without diabetes. Here in this pre-specified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (−10.2%), waist circumference (−7.7 cm) and waist-to-height ratio (−6.9%) versus placebo (−1.5%, −1.3 cm and −1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (<30, 30 to <35, 35 to <40 and ≥40 kg m−2) there were lower rates (events per 100 years of observation) of serious adverse events with semaglutide (43.23, 43.54, 51.07 and 47.06 for semaglutide and 50.48, 49.66, 52.73 and 60.85 for placebo). Semaglutide was associated with increased rates of trial product discontinuation. Discontinuations increased as BMI class decreased. In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo. Weight loss was sustained over four years.
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