Docs Worry Not Enough Known About GLP-1s and Teens

 About 20% of adolescents have obesity, a figure that is expected to rise over the next few decades. And while popular weight loss drugs are a potential tool for physicians caring for these young people, many doctors are not yet sure that these drugs are ready to be front-line treatments. 

"Over the last several decades we’ve had a significant increase in youth-onset obesity," said Sheela Magge, MD, chief of pediatric endocrinology at Johns Hopkins Medicine in Baltimore.

Along with obesity, Magge said, comes complications such as type 2 diabetes, high blood pressure, and high cholesterol. Childhood and adolescent obesity may also lead to poor self-esteem and clinical depression. 

“I think it’s a crisis, honestly," says Susma Shanti Vaidya, MD, MPH, a general pediatrician in Washington, DC.

“And what we worry about are children who are developing cardiometabolic disease,” said Vaidya, who is also the interim medical director of the IDEAL Clinic at Children’s National Hospital, a weight management clinic for children and adolescents. She said she agrees that we need long-term studies in children and adolescents with obesity on the risks of these medications, but she stresses that deciding to use them is a risk-benefit calculation, weighing on one side the “very real health risks from obesity.”

“I’m not as worried about the long-term side effects of these medications in children with comorbidities and disease which is affecting their health now, given the fact that the data so far supports the efficacy and safety of these medications,” Vaidya said via email through a spokesperson. 

Magge adds, “If you think of a 60- or 70-year-old getting diabetes and then having complications 10 years, 20 years later, that’s bad enough. But what happens to my patient who gets type 2 diabetes when she’s 10? Will she have a heart attack in her late twenties?”

These days, there are a variety of medications used to treat obesity in children, including the drug class of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) such as liraglutide (Saxenda) and semaglutide (Wegovy). Tirzepatide (Zepbound and Mounjaro) is currently under study for weight loss in adolescents with obesity but is not approved for this indication by the US Food and Drug Administration (FDA). A variety of other medications are used for weight management in children and teens with obesity as well. 

In 2023, the American Academy of Pediatrics issued guidelines for the evaluation and treatment of children and adolescents with obesity. The guidelines recommend that pediatric health care providers should offer teens weight loss pharmacotherapy if they have a body mass index (BMI) ≥ 95th percentile. Those recommendations, however, say the drugs should be used “according to medication indications, risks, benefits, as an adjunct to health behavior and lifestyle treatment.” 

Guidelines also suggest that practitioners may consider offering children with obesity who are age 8-11 similar pharmacotherapy options under the same circumstances. 

Research has suggested a benefit of GLP-1 RAs for children and adolescents with obesity.

“I’ve never seen weight loss like this,” Magge said, referring to GLP-1 RAs. For some of her young patients for whom insurance has covered a GLP-1 RA, “…It’s actually getting to the point where they’re at least coming back towards being on the growth chart … The obesity was so severe, they were off the growth charts.” 

But what do doctors in general really think about prescribing pharmacotherapy to children and adolescents with obesity? In response to one question in a broad-reaching Medscape survey of doctors, published in September, 80% of participants (N = 1017 full- or part-time US practicing physicians) answered no when asked, “Is enough known about obesity meds’ risk to adolescents?” 

Although the survey addressed general doctors, Medscape wanted to drill down further and find out what pediatricians and pediatric specialists really feel about prescribing pharmacotherapy for weight loss to children and teens. Are there concerns about short- and long-term side effects? Are those potential risks outweighed by the serious outcomes of untreated obesity? How well educated are pediatric care providers about weight loss medications? Medscape reached out to some pediatric specialists for their thoughts.

Side Effects

For the GLP-1 RAs, side effects are mainly gastrointestinal, says Stephanie Green, MD, a pediatric endocrinologist who is also certified in obesity medicine at Johns Hopkins Medicine. Nausea is the most common adverse effect; vomiting, constipation, and/or diarrhea are other complications. Taking GLP-1 RAs can also increase one’s risk for pancreatitis and/or gallbladder disease. 

Children may also experience headaches or fatigue. Finally, there is a potential increased risk for thyroid cancer, Green said, noting that it’s unclear whether that risk, found in mice, really translates to humans. Often the side effects abate the longer a patient is on the medication. 

Vaidya, who is also board certified in obesity medicine, said she is not overly concerned about the long-term effects of GLP-1 RAs in children and teenagers, as the medications have been around for a while (for example, liraglutide was approved in 2020 for weight management in teens with obesity age 12 and up). She points to research (on adults) that examined 4-year outcomes on semaglutide and which was reassuring in terms of safety and tolerability. 

There need to be long-term follow-up studies, she said, but she would hesitate to say not to use the medications while we await those studies.

Green said that it is prudent to use caution in the face of the unknown, but when she sees a 10-year-old with type 2 diabetes and a “burned-out pancreas,” she’s not going to just watch without trying an intervention. 

She added, “We need to think about that particular child — what we’re worried about, what we’re trying to treat, what are the concerns of starting that child on medication? And so, it’s very individualized medicine.”

‘Game Changer’

Vaidya comes to the field of adolescent obesity medicine with a different perspective from the average primary care provider's. While she is a general pediatrician, she’s been practicing pediatric obesity medicine since 2006.

“So, I have had the privilege of seeing this evolution in treatment options and better understanding obesity as a disease,” she said. 

In her view, there remains a pervasive belief among medical professionals, insurance companies, and laypeople that obesity results from a failure of personal responsibility or willpower. If we keep thinking about obesity this way, “it may feel like, ‘well, why would you want to put someone on a medication if all they need to do is, you know, see a dietitian once a month or something?’”

There are a lot of data to suggest that for children who have more severe forms of obesity, lifestyle changes alone are unlikely to lower BMI and sustain it, Vaidya says. She is excited by new developments in the field. “I think [with] a lot of these medications, we have the opportunity to help kids in a really substantive way; to have kids who come to you and have been struggling, have been making lifestyle changes, have been working really hard and are not seeing improvement in some of their comorbidities … and they are able to start some of these medications and make a lot of progress.”

Vaidya referred to pharmacotherapy as a “game changer” in the treatment of childhood obesity.

Shifting Culture and Attitudes

Magge said insurance rarely covers GLP-1 RAs for adolescents with obesity unless they have diabetes. And for her patients on Medicaid, the drugs are not getting approved at all. 

It’s a health disparities issue, she said — “I mean, $1600 a month” for medication. It’s a very exclusive group that can afford that, she added.

Vaidya, however, is seeing a shift in insurance coverage. In the beginning, when Wegovy was first FDA-approved in 2022 for weight loss in children and teens with obesity ages 12 and up, she saw very few private insurance companies covering it, but now she sees more coverage. 

The 2023 American Academy of Pediatrics guidelines are playing an important role in helping pediatricians get more comfortable with using pharmacotherapy for weight management, Vaidya said.

Magge, however, has seen in the community that general pediatricians are not comfortable prescribing pharmacotherapy for teens with obesity and will refer these patients out. She doesn’t blame them, but they’ll eventually have to start prescribing the drugs, she said.

Vaidya noted that there needs to be support in the primary care setting for providing resources like access to a nutritionist; these medications shouldn’t be used in isolation, she said. Green added that there are year-long fellowships in obesity medicine and online education opportunities too.

Understand Use but Need to Study

Dan Cooper, MD, first author on an article about the unintended consequences of GLP-1 RAs in adolescents and children, said about the Medscape survey result, “They’re right. We don’t know.”

Cooper is the interim executive director for the University of California Irvine Institute for Precision Health. A pediatric lung disease specialist who studies how physical activity affects growth and development in health and disease in children, he said that he understands his pediatric colleagues’ desire for a new weight management tool. 

He empathizes with their desire to help. At an office visit, they have only a short time with a patient and don’t have time to dissect the multifactorial nature of the child’s obesity. 

He stressed that he is not against the use of pharmacotherapy in children and teens with obesity but would like more study. For example, the role of physical activity and nutrition in kids is a bit complex, he says, because it takes place over years. 

“So now we’re going to reduce appetite and reduce food intake — which is what happens with these drugs — at a critical point in growth and development. If we start giving them in large numbers to a pediatric age group, what are the longer-term consequences? We’re not going to see them right away,” he said. 

Vaidya expressed concern that children and teens who are given these medications may develop overly restrictive eating patterns. When prescribing weight loss pharmacotherapy, good follow-up is needed, she said. Doctors must make sure that patients continue eating healthy meals three times a day, that they not skip meals, and that they not get “overly focused on the number on the scale.”

With that said, Vaidya doesn’t expect her patients to be on weight management pharmacotherapy for 10 years “because I don’t think it’s going to work” for that long. 

The field is changing, she said. New medications are coming out. For example, there is an ongoing study of tirzepatide in adolescents. “The data in the adults is really… impressive.” She said in an email that there is a need for long-term studies in children and teens, but the data so far “supports the efficacy and safety of these medications.” 

Green argues that there is “enough data, there’s enough publications. It’s enough in the media and in conferences and in journal clubs now that every physician should be aware that this is not just a lifestyle choice, but a systematic issue in the presence of an obesogenic environment.”

Do we really know long-term data? Magge said, “We don’t. And I would love to get that more long-term data. But you also have to weigh that in regard to the risks of severe obesity in a child and having complications of their obesity.”

Cooper said he supports pharmacotherapy as part of a multidisciplinary approach to obesity management. However, he cautioned that the data may not be so robust in favor of pharmacologic treatment.

One key study, “Once-Weekly Semaglutide in Adolescents with Obesity,” found that 73% in the semaglutide group had weight loss of 5% or more, as compared with 18% in the placebo group, which included a lifestyle intervention (estimated odds ratio, 14.0; 95% CI, 6.3-31.0; P < .001). However, he noted that the lifestyle intervention was not comprehensive, and the study authors did not verify that children followed the lifestyle advice. 

“It was really anemic,” he said of the lifestyle intervention. “… It wasn’t what I would call — as someone who studies this — a decent intervention.”

Asked about the nature of the lifestyle intervention used in the study, author Daniel Weghuber, MD, wrote in an email:

“The study protocol for[e]saw a defined number of counseling visits. Exercise and dietary habits were not assessed as outcomes. Although this would have been very informative the number of contact hours was according to current conservative treatment guidelines of health behavior and lifestyle treatment (26-52 per year). Future studies will hopefully fill in the gaps.”

It's hard to build an adequate lifestyle intervention, Cooper said. “So that’s why the American Academy of Pediatrics, which is, you know, traditionally disease-oriented, ‘let’s-fix-it-with-a-drug,’ has embraced these medicines.

“But still, as you point out in the survey, the physicians, the clinicians are aware enough to know we really don’t know what the long-term consequences are.”

"We always counsel for lifestyle modifications first," Magge said. But many of her patients already have severe obesity. They’ve tried lifestyle modifications for at least 6 months, and they still have a BMI greater than the 99th percentile. The obesity she treats is often “off the charts.”

“I’m trying to prevent complications,” she said.

https://www.medscape.com/viewarticle/docs-worry-not-enough-known-about-glp-1s-and-teens-2025a100001w