GLP-1 receptor agonists may help teens with obesity maintain weight loss
Click Here to Manage Email Alerts
Teens with severe obesity who lost weight maintained more of their weight loss with use of a GLP-1 receptor agonist plus lifestyle therapy compared with lifestyle therapy alone, according to study findings published in Obesity.
In findings from a randomized controlled trial, youths with severe obesity who achieved a 5% or greater BMI reduction during the trial’s run-in phase and were randomly assigned to exenatide extended-release (Bydureon, AstraZeneca) had a smaller BMI increase after weight loss than those randomly assigned to placebo. However, the difference between the two groups was not statistically significant.
“Though our primary endpoint did not reach statistical significance, the results clearly show that exenatide improved weight-loss maintenance in adolescents with severe obesity,” Aaron Kelly, PhD, professor of pediatrics and co-director of the University of Minnesota Center for Pediatric Obesity Medicine, told Healio. “Pediatricians should consider using anti-obesity medication as a treatment option to assist teens with obesity in preventing weight regain.”
Kelly and colleagues enrolled 100 youths aged 12 to 18 years with a BMI 1.2 times higher than the 95th percentile of their CDC-derived normal level by age or sex, or a BMI higher than 35 kg/m2. Participants took part in a run-in phase with 4 to 8 weeks of meal replacement therapy. Sixty-six participants who achieved a BMI decrease of at least 5% by the end of the run-in phase were randomly assigned 1:1 to 2 mg exenatide extended-release or placebo weekly for 1 year. Youths in both groups received lifestyle therapy during the study. The primary outcome was the mean percent change in BMI from randomization to 1 year. Body composition, blood pressure, fasting lipid profiles, glucose, HbA1c and quality of life were analyzed as secondary outcomes.
At 1 year, the treatment group had a mean BMI increase of 4.6%, and the placebo group’s BMI increased 10.1%. The estimated treatment difference between the two groups was not statistically significant. Within the per-protocol population, which included those who maintained their assigned treatment without major deviations and completed the 52-week follow-up, the exenatide group had a lower BMI increase compared with placebo (mean difference, –5.7 percentage points; 95% CI, –10.9 to –0.5; P = .03).
“We were surprised to see the degree of weight regain in both the medication and placebo groups,” Kelly said. “These results highlight how difficult it is for adolescents to keep weight off once they lose it.”
Those taking exenatide had an increase of 8 bpm in heart rate from randomization to 1 year compared with a 1 bpm increase for placebo (P = .03). The exenatide group had a 0.6-point decrease in triglyceride to HDL cholesterol ratio compared with a 0.2-point increase for placebo (P = .05). No other significant changes in cardiometabolic risk factors were observed.
The percentage of participants who experienced adverse events was similar in both groups. Nausea, vomiting and diarrhea were more common in the exenatide extended-release group compared with placebo.
“The current trial demonstrated the potentially useful role of GLP-1 receptor agonists to enhance weight-loss maintenance in the management of severe adolescent obesity, although we did not demonstrate a statistically significant result,” the researchers wrote. “It is possible that more potent GLP-1 receptor agonists would have more robust results, given the data on weight loss in adults. Furthermore, the high degree of heterogeneity in treatment effect highlights the need for identifying predictors of response to pharmacotherapy for weight-loss maintenance.”
For more information:
Aaron Kelly, PhD, can be reached at kelly105@umn.edu.
Perspective
Back to Top
What treatment options are available for our adolescent patients with severe obesity? Lifestyle therapy is necessary but almost always insufficient. While bariatric surgery has demonstrable efficacy, its use can be limited by the availability of specialized pediatric surgical programs. What, then, about pharmacotherapy?
Prior to the availability of liraglutide in late 2020, the FDA-approved options for adolescents, orlistat and phentermine, were of limited utility, having marginal efficacy and/or problematic side effects. On the basis of their effectiveness and tolerability in adult type 2 diabetes and obesity, liraglutide and other GLP-1 receptor agonists have the potential now to improve pediatric obesity management dramatically.
While the study by Fox and colleagues did show that the GLP-1 receptor agonist exenatide extended-release was reasonably well tolerated in adolescents with severe obesity, it did not conclusively demonstrate that exenatide extended-release improved the maintenance of diet-induced BMI reduction. This is disappointing, but not surprising. Exenatide and exenatide extended-release were groundbreaking treatments for type 2 diabetes over the past 20 years, but more potent and easier to use GLP-1 receptor agonists represent the future of this medication class.
Collapse
Click Here to Manage Email Alerts