GLP-1 receptor agonists may be 'critical' weight-loss tool in severe pediatric obesity
NASHVILLE, Tenn. — Adolescents with severe obesity who struggle with weight loss may derive the most benefits from a combination of intensive lifestyle modification and an injectable GLP-1 receptor agonist, according to a speaker here.
GLP-1 receptor agonists are primarily prescribed for adults with type 2 diabetes for improving glycemic control, with one agent, liraglutide (Saxenda, Novo Nordisk), FDA approved for the treatment of adult obesity, Aaron S. Kelly, PhD, co-director of the Center for Pediatric Obesity Medicine at the University of Minnesota, said during a presentation at ObesityWeek 2018. Studies suggest that GLP-1 receptors in the hypothalamus, activated by the medication, also reduce appetite, whereas evidence about the class’ ability to slow gastric motility is mixed, he said.
“Preliminary results suggest that GLP-1 receptor agonists, which target appetite and satiety, may be safe and effective for treating obesity in adolescents,” Kelly told Endocrine Today before his presentation. “The number of youths with severe obesity (a BMI at 120% of the 95th percentile or higher) in the U.S. is near 5 million. Most are unable to lose a meaningful amount of weight with lifestyle changes alone because the body fights back against attempts at energy restriction.”
Weight-loss medications, Kelly said in an interview, can alter the physiology of the energy regulatory system in a way that helps individuals lose weight and keep it off. Yet, only one obesity medication, orlistat (Alli, GlaxoSmithKline), is approved for chronic use in adolescents aged at least 12 years. That therapy is not widely used, he said, because of modest efficacy and notable side effects.
Bariatric surgery, another option for adolescents with severe obesity, is even more rarely used, Kelly said. All the while, teens with severe obesity typically struggle the most to both lose weight and maintain their weight loss for any extended period, he said.
“So, we need to think about filling the gap there,” Kelly said. “We need to get serious about exploring and utilizing biologically based treatments that can help push back against these mechanisms.”
New pediatric data coming
Kelly said two large adolescent clinical trials evaluating GLP-1 receptor agonists are projected to conclude before the end of 2019, which should shed light on safety and efficacy in the pediatric population.
The adolescent high-dose liraglutide trial, a randomized controlled trial, includes 220 adolescents with obesity aged 12 to 17 years randomly assigned to liraglutide or placebo for 1 year, with a primary outcome of change in BMI. The study is sponsored by Novo Nordisk.
A second study, funded by the National Institute of Diabetes and Digestive and Kidney Diseases and conducted at the University of Minnesota, will enroll 100 adolescents with severe obesity and is designed to assess the ability of GLP-1 receptor agonists to enhance weight-loss maintenance, Kelly said. Teens who are successful at losing at least 5% of BMI over 2 months will be randomly assigned to once-weekly exenatide (Bydureon, AstraZeneca) or injectable placebo for 1 year, with change in BMI as the primary outcome.
“This is exciting because in the next year or so we’re going to have, for pediatrics, what will be considered a lot of data on the safety and efficacy [of GLP-1 receptor agonists],” Kelly said. “Prime time [for these medications in adolescents] is not that far away.”
However, like all treatments, weight-loss response is highly variable, Kelly said.
“We need to have a keen eye on identifying predictors of response to GLP-1s to enhance outcomes and reduce risk for pediatric patients using this class of medication,” Kelly told Endocrine Today.
Future of GLP-1s
With more research and stronger safety data, GLP-1 receptor agonists may become part of the weight-loss tool box for adolescents with severe obesity in the not so distant future, Kelly said.
“We need the safety and efficacy data, so pediatricians have something to hang their hat on and have some confidence about [prescribing],” Kelly said. “If we can be very intentional about identifying predictors of response, perhaps the comfort level will go up even more.
“For adolescents with severe obesity, because of the refractory nature of this chronic disease, first-line treatment ought to be intensive lifestyle modification counseling along with pharmacotherapy, and I think GLP-1’s will be a prominent aspect of that,” Kelly said. – by Regina Schaffer
Kelly AS. GLP-1 receptor agonists for the management of pediatric obesity: Ready for prime time? Presented at: ObesityWeek 2018; Nov. 11-15, 2018; Nashville, Tenn.
For more information:
Aaron S. Kelly, PhD, can be reached at the Center for Pediatric Obesity Medicine at the University of Minnesota, 2450 Riverside Ave., 6th Floor, East Building, Delivery Code 8952A, Minneapolis, MN 55454; email: firstname.lastname@example.org.
Disclosure: Kelly reports he has received research support from Astra Zeneca and serves as an unpaid consultant for Novo Nordisk, Orexigen, and Vivus Pharmaceuticals.