GLP-1RA weight-loss drugs may be dangerous to children, UCI researchers warn

 
August 29, 2023
UCI Health pediatrician and childhood exercise expert Dr. Dan Cooper  is concerned with the use of GLP-1 medications for children and adolescents.

UCI Health pediatrician Dr. Dan Cooper worries about children and adolescents taking GLP-1RA weight-loss drugs. “Unlike in adults, children and adolescents need energy and sufficient calories, not only for physical activity, but for growth and development."

Irvine, Calif. — A team of clinicians, exercise scientists, pharmaceutical scholars, ethicists and behavioral experts at the University of California, Irvine, are raising concerns that treating childhood obesity and type 2 diabetes with weight-loss drugs using glucagon-like peptide-1 receptor agonists (GLP-1RA) may have unintended and adverse consequences for children's health.

Their commentary, Unintended Consequences of Glucagon-like Peptide-1 Receptor Agonists Medication in Children and Adolescents – A Call to Action, was published in the Journal of Clinical and Translational Science. The lead author is Dan M. Cooper, MD, distinguished professor in the Department of Pediatrics at the UCI School of Medicine.

In the commentary, the team said this class of medications is transforming the care of obesity and type 2 diabetes in adults and noted recent studies showing they are having similarly powerful weight-loss effects in children and adolescents.

Given the intractable epidemic of pediatric obesity and the associated rise in type 2 diabetes in young people — made worse by COVID-19 pandemic-related shutdowns and disruptions in opportunities for children to play and exercise — the new class of medications will certainly benefit children with morbid obesity and type 2 diabetes, they said. Ironically, it is the unprecedented success of these medications to help people lose weight that has team members worried, saying that overuse and abuse among young people is inevitable.

“Our major concern is the unbalance and inappropriate reductions in calorie or energy intake associated with these weight-loss drugs," said Cooper, associate director of the UCI Institute for Clinical and Translational Science and interim director of the UCI Institute for Precision Health. “Unlike in adults, children and adolescents need energy and sufficient calories — not only for physical activity, but for growth and development."

The balance of energy intake (diet) and energy expenditure (physical play and exercise) influences a child’s growth and health across their life span, they noted, adding that any change in the balance of these two factors can adversely impact health later in life. For example, optimal levels of both diet and exercise increases bone mineralization during childhood, a critical period of growth and development, and lessens their risk of osteoporosis and bone fractures later in life.

Potential for misuse

The team also pointed out the likelihood of abuse among patients with diagnosed eating disorders, as well as children and adolescents involved in competitive sports like wrestling, martial arts, gymnastics and ballet.

“The benefit vs. cost (economic and quality of life) relationship of long-term use in youth needs to be carefully studied," said co-author Jan D. Hirsch, dean of the UCI School of Pharmacy and Pharmaceutical Sciences. “With the increase in social media, young people are already exposed to a diet culture and body images which may not be attainable and, ultimately, unhealthy. These drugs administered without proper supervision could cause a minefield of health and emotional problems for children as they age.”

Cooper also observed that pediatric obesity has become epidemic in large measure because of environments without adequate venues for safe play and exercise for children and adolescents, coupled with the availability of popular, inexpensive, high-calorie fast-foods. Not surprisingly, the epidemic of poor physical fitness and obesity has disproportionately affected underrepresented minorities.

With the high efficacy and growing popularity of these medications, drug manufacturers are quickly developing oral forms of the injectable drugs, which researchers believe could limit oversight and result in cases of abuse. Anecdotal clinical experience suggests that there is already considerable knowledge within the pediatric population about the GLP-1RA drugs' effectiveness as satiety medications that aid in weight loss, which is not helped by their widespread use as documented in the popular media.

“News about GLP-1RA agonists has infiltrated social media outlets and is being spoken about by celebrities, fashion models and influencers," said Emma Cooper, MD, a resident physician in the Department of Psychiatry & Human Behavior at the UCI School of Medicine. "It’s reasonable to assume that as access becomes easier, more children will engage in unsupervised use of GLP-1RA agonists in order to facilitate reaching societal beauty standards."

She added, "As the rate of mental health disorders, including eating disorders, continues to rise, healthcare providers should be screening for, and intervening on, inappropriate use of these medications.”

Researchers also believe children's health could be threatened, not only by the rise of counterfeit drugs that have been well documented, but also by illegitimate access to them through the internet.

Plan of action

The UCI team outlined a call-to-action based on their past research and clinical experience with exercise, diet and obesity prevention. They hope to target the National Institutes of Health's network of academic centers, such as UCI, that have received Clinical and Translational Science Awards at National Center for Advancing Translational Sciences hubs across the nation.

Their call-to-action includes:

  • Build and support multidisciplinary teams of frontline clinicians, community partners, physiologists and behavioral and pharmaceutical scientists to address the knowledge gap in GLP-1RA effects in children and adolescents.
  • Address the translational bioethics research issues that will result from approval of pediatric formulations of the GLP-1RA medications in particular, and in general, that have evolved from the medicalization of health conditions like pediatric obesity.
  • Engage and improve the quality and accessibility of relevant real-world data such as school-based physical fitness testing, mandated in 16 states and covering about 60% of U.S. school children.
  • Work with the U.S. Food and Drug Administration and other agencies to update guidelines for lifestyle interventions in pediatric clinical trials to incorporate state-of-the-art approaches to quantifying, monitoring and evaluating physical activity, adherence to diet, and to the accurate measurement of body composition beyond the current reliance on body mass index (BMI), a suboptimal metric of overweight and obesity in adolescents.
  • Elevate and enhance training of the clinical trial workforce to provide state-of-the-art understanding of effective lifestyle interventions. Such training should also target primary care pediatricians whose exposure to exercise and nutritional science is currently quite limited.
  • Develop, demonstrate and disseminate learning modules about the medications, their appropriate uses and possible abuse to educate school personnel (teachers, coaches), parents, school-aged children, primary care pediatricians and child mental health professionals.

This research and subsequent call-to-action was part of a multidisciplinary team effort across the University of California, Irvine, that included the School of Medicine, the School of Pharmacy and Pharmaceutical Science and the UCI Institute for Clinical and Translational Science.

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