Adults with obesity, preexisting CVD maintain weight loss with semaglutide at 4 years
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Key takeaways:
- Of adults receiving semaglutide, 44.2% lost at least 10% of their body weight at 2 years.
- Those in the semaglutide group reduced their waist circumference 7.7 cm at 4 years.
Adults with obesity lost 10.2% of their body weight at 4 years with the GLP-1 receptor agonist semaglutide, according to an analysis of data from the SELECT trial.
As Healio previously reported, the SELECT trial randomly assigned 17,604 adults with obesity and established cardiovascular disease to once-weekly semaglutide 2.4 mg (Wegovy, Novo Nordisk) or placebo. In the trial’s primary findings, the semaglutide group had a 20% lower risk for a CV event compared with placebo. Patients in the semaglutide group also lost a mean 9.4% of their body weight at 2 years. In new data published in Nature Medicine and presented at the European Congress on Obesity annual meeting, adults receiving semaglutide were able to maintain their weight reduction as well as a decrease in waist circumference and waist-to-height ratio for up to 4 years.
“These data, representing the longest clinical trial of the effects of semaglutide vs. placebo on weight, establish the safety and durability of semaglutide effects on weight loss and maintenance in a geographically and racially diverse population of adult men and women with overweight and obesity but not diabetes,” Donna H. Ryan, MD, professor emerita at Pennington Biomedical Research Center in Baton Rouge, Louisiana, and colleagues wrote. “The implications of weight loss of this degree in such a diverse population suggests that it may be possible to impact the public health burden of the multiple morbidities associated with obesity.”
In SELECT, adults with obesity and CVD and without diabetes were randomly assigned, 1:1, to semaglutide or placebo. All participants were treated with evidence-based recommendations and received lifestyle counseling. Change in body weight, waist circumference and waist-to-height ratio was assessed at 2, 3 and 4 years. Researchers examined the percentage of participants who had a change in BMI category at 2 years. Severe adverse events were assessed by BMI category.
Reductions in weight, waist circumference
At 4 years, adults receiving semaglutide lost 10.2% of their body weight compared with a 1.5% weight loss for those receiving placebo (P < .0001). At 2 years, 67.8% of the semaglutide achieved a 5% weight loss, 44.2% lost 10% or more of their body weight, 22.9% lost at least 15% of their body weight, 11% lost 20% or more of their body weight and 4.9% of adults achieved a 25% or greater weight reduction.
The semaglutide group had a 7.7 cm reduction in waist circumference at 4 years compared with a 1.3 cm decline for the placebo group (P < .0001). Among adults with a baseline BMI of less than 35 kg/m2, 41.2% of adults receiving semaglutide achieved a waist circumference below their sex- and race-specific cutoff point at 2 years vs. 18% of the placebo group. Waist-to-hip ratio declined by 6.9% in the semaglutide group at 4 years compared with a 1% reduction for the placebo group.
At 2 years, 12% of adults with semaglutide reduced their BMI to less than 25 kg/m2 vs. 1.2% of those receiving placebo. The percentage of adults with obesity as defined by a BMI of 30 kg/m2 declined from 71% at baseline to 43.3% at 2 years in the semaglutide group.
Within all obesity classes, adults receiving semaglutide had fewer severe adverse events than those receiving placebo. Researchers also found no difference in hepatobiliary or gastrointestinal severe adverse events between the semaglutide and placebo groups in any obesity class.
“The analysis did reveal that tolerability may differ among specific BMI classes, since more discontinuations occurred with semaglutide among lower BMI classes,” the researchers wrote. “Potential contributors may include a possibility of higher drug exposure in lower BMI classes, although other explanations, including differences in motivation and cultural mores regarding body size, cannot be excluded.”
More studies needed on physiology
The researchers said adults with a BMI of 30 kg/m2 or less lost less weight than those with a higher BMI and hypothesized that those adults may have had a lower percentage weight loss as they may be closer to reaching a set point where their weight “is in harmony with the genetic and environmental determinants of body weight and adiposity.”
“The cardiometabolic benefits of weight loss are driven by reduction in the abnormal ectopic and visceral depots of fat, not by reduction of subcutaneous fat stores in the hips and thighs,” the researchers wrote. “The phenotype of cardiometabolic disease but lower BMI may be one where reduction of excess abnormal and dysfunctional body fat does not require as much body mass reduction to achieve health improvement. We suspect this may be the case and suggest further studies to explore this aspect of weight-loss physiology.”
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