Adolescents who lose weight more quickly tend also to improve related habits, such as diet: pediatric endocrinologist at VUMC.

Pediatricians have a better tool for reducing childhood obesity following a key study in NEJM Evidence that found the combination of phentermine and topiramate significantly reduces body mass index (BMI) in pediatric patients.

The study, which looked closely at the response to daily dosing, came following calls for further investigation of medications for treating obesity in younger populations, said Ashley Shoemaker, M.D., a pediatric endocrinologist at Monroe Carell Jr. Children’s Hospital at Vanderbilt and a site principal investigator for the study.

“It really helps our ability to understand their effects on kids, who may be going through puberty, having active growth. They may have different safety profiles than adults.”

“The FDA has been pushing companies to do these pediatric trials. Previously, we were forced to start using medications approved for adults, based on adult studies,” said Shoemaker, who called the study “exciting.”

“It’s exciting because it really helps our ability to get insurance coverage on these medications and to understand their effects on kids, who may be going through puberty, having active growth. They may have different safety profiles than adults.”

Repurposed Drugs Give Results

When the drug-combination’s efficacy was compared to lifestyle modifications alone, the findings helped gain FDA approval for oral phentermine/topiramate for chronic weight management in children 12 years and older – a welcome approval for an oral weight-loss medication, Shoemaker said. Previously, injections were required to reach similar results.

According to the publication, researchers split into three groups a total of 223 pediatric patients with an average age of 14 years. One group received placebo. The remaining groups received either a mid- (7.5 mg/46 mg) or high-dose (15 mg/92 mg) capsule of the phentermine/topiramate combination daily. All participants received lifestyle therapy.

After about a year, participants in the medication’s mid- and top-dose groups had BMI measurements that were lower by 8-10 percentage points when compared to the placebo group. Participants in both treatment groups experienced significantly lower levels of circulating triglycerides and HDL cholesterol.

Need for Data and Guidance

Shoemaker noted that both phentermine and topiramate have been long approved for other indications, and some pediatricians also have been using them off-label to treat childhood obesity in cases where other interventions have failed. The combination, however, had not been rigorously tested in pediatric patients.

“We just didn’t have the data. That was always going to limit widespread use,” Shoemaker said.

With childhood obesity becoming commonplace, the American Academy of Pediatrics recently released its first clinical practice guidelines involving evaluation and treatment of the condition. A medical approach to childhood obesity is one of several strategies the academy endorsed. However, consensus on what comprises a successful treatment has been elusive.

“Although consensus has been established in adults that a loss of 3- to 5-percent of body weight is considered clinically meaningful, a similar threshold of BMI reduction in children and adolescents has yet to be identified and agreed upon,” wrote Shoemaker and colleagues in their NEJM study.

Support For Younger Patients

Complicating the issue, Shoemaker said, are practical challenges that come with enrolling children or teens in weight-loss trials.

“The placebo groups are always hard in these studies,” she said. “When we do the adult studies, typically both treatment and placebo groups will lose weight because everyone is open to all the interventions. In pediatric studies, we tend to see that the placebo groups actually gain weight.”

“Kids who received the study drug who were starting to see weight loss often got more motivated about the other changes.”

Shoemaker said it’s a struggle to get children and teens to lose weight with lifestyle interventions alone, even outside of trials. Adjunct medication could be helpful for some patients.

“We found kids who received the study drug who were starting to see weight loss often got more motivated about the other changes, like their diet or going to the gym, because they were seeing success,” she said. “A lot of our patients struggle if they’re not seeing immediate positive feedback. Developmentally, kids and teens are not great with long-term rewards.”

More Children Could Benefit

In contrast, Shoemaker says certain pediatric subpopulations are highly motivated to participate in weight-loss trials, regardless of the intervention.

“A lot of my clinical studies focus on very specific causes of obesity, including brain tumors or genetic syndromes like Prader-Willi syndrome, and trying to figure out which medications work for them. Those groups tend to be more motivated to stay in studies and to help others,” she said.

Regardless of the underlying cause, Shoemaker said there is a clear need to enroll children in weight-loss trials to expand options.

“The next stage to study is 6- to 11-year-olds. Very few weight loss drugs have been tried in prepubertal patients, where we need to be even more careful about whether we’re affecting growth and development,” she said. “That may require longer-term studies to look at growth and bone, which can take years to see side effects.”

The investigators are hopeful that this momentum continues to prevent related health effects from becoming worse. As childhood obesity rates have risen in recent years, Shoemaker and others have seen a corresponding rise in type 2 diabetes among children.

“A lot of kids struggled with weight gain during the pandemic. We know this weight gain is important medically. We’re seeing kids struggle with type 2 diabetes, fatty liver, and we’re looking for new ways to treat these complications of obesity.”

About the Expert

Ashley Shoemaker, M.D.

Ashley Shoemaker, M.D., M.S.C.I., is assistant professor of pediatrics at Vanderbilt University Medical Center. Her clinical interests include early onset obesity, hypothalamic obesity and pseudohypoparathyroidism.