Irvine, Calif., Aug. 28, 2023 — The use of glucagon-like peptide-1 receptor agonists in weight-loss drugs like Ozempic and Wegovy to treat childhood obesity and type 2 diabetes may have unintended and adverse consequences for children’s health, according to a team of clinicians, exercise scientists, pharmaceutical scholars, ethicists and behavioral experts at the University of California, Irvine.

Their commentary, Unintended Consequences of Glucagon-like Peptide-1 Receptor Agonists Medication in Children and Adolescents – A Call to Action, appears as a perspective article in the Journal of Clinical and Translational Science. Its main author is Dr. Dan M. Cooper, distinguished professor of pediatrics in the UCI School of Medicine.

In the perspective, the team noted that the GLP-1RA class of medications is transforming the care of obesity and type 2 diabetes in adults and that recent studies have indicated similar powerful effects in children and adolescents. Given the intractable pediatric obesity epidemic and associated rise in type 2 diabetes in youth – made worse by the COVID-19 pandemic related shutdowns and disruptions in opportunities for exercise and play in youth – this new class of medications will certainly benefit children with morbid obesity and type 2 diabetes. Ironically, it is the unprecedented success of these medications that worries the team, who believes that their overuse and abuse among youth 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 (such as physical play and exercise) influences a child’s growth and health across their lifespan, and any change in the balance of these two factors can adversely impact health much later in life. For example, optimal levels of both diet and exercise increase bone mineralization during childhood, a critical period of growth and development. This lessens their risk of osteoporosis and bone fractures later in life.

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

“The benefit versus cost relationship of long-term use in youth, both economic and quality of life, needs to be carefully studied,” said Jan D. Hirsch, one of the co-authors and dean of the School of Pharmacy and Pharmaceutical Sciences at UCI. “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 noted that conditions like pediatric obesity have become epidemic in large measure because of environments without adequate venues for safe play and exercise coupled with the availability of popular, inexpensive and high-calorie fast-foods. Not surprisingly, the epidemic of poor physical fitness and obesity has impacted underrepresented minorities disproportionately.

With the growing efficacy and popularity of these medications, drug manufacturers are quickly developing oral forms of the drugs, which researchers believe could limit oversight and cause cases of abuse. Anecdotal clinical experience suggests that there is already widespread knowledge in the pediatric population about the GLP-1RA effectiveness as satiety medications aiding weight loss, not helped by apparent widespread use 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. 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,” said Dr. Emma Cooper, a resident physician in psychiatry and human behavior in the UCI School of Medicine. “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 believe appropriate pediatric health could also be threatened, not only by the rise of counterfeit drugs that have been well documented but by illegitimate access through the internet.

As a result of their research and clinical experience with exercise, diet and obesity prevention, the UCI team outlined a call-to-action. Targeting the National Institutes of Health network of academic centers, like UCI, that are recipients of Clinical and Translational Science Award hubs across the nation, the call-to-action includes:

1. Building and supporting 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.

2. Addressing 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.

3. Engaging and improving the quality and accessibility of relevant real-world data such as school-based physical fitness testing, mandated in 16 states covering around 60 percent of American school children.

4. Working with the FDA and other agencies to update guidelines for lifestyle interventions in pediatric clinical trials that incorporate state-of-the-art approaches to quantifying, monitoring and evaluating physical activity. These guidelines should include adherence to diet and accurate measurement of body composition beyond the current reliance on the body mass index, a suboptimal metric of overweight and obesity in adolescents.

5. Elevating and enhancing training of the clinical trial workforce on 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 limited.

6. Developing, demonstrating and disseminating learning modules for school personnel, parents, school-aged children, primary-care pediatricians and child mental health professionals about the GL1-RA medications, their appropriate uses and possible abuse.

This research and subsequent call-to-action was part of a multi-disciplinary team effort including the UCI School of Medicine, UCI School of Pharmacy and Pharmaceutical Science and the UCI Institute for Clinical and Translational Science. It was supported by the National Institutes of Health.

About the UCI School of Medicine: Each year, the UCI School of Medicine educates more than 400 medical students and nearly 150 PhD and MS students. More than 700 residents and fellows are trained at the UCI Medical Center and affiliated institutions. Multiple MD, PhD and MS degrees are offered. Students are encouraged to pursue an expansive range of interests and options. For medical students, there are numerous concurrent dual degree programs, including an MD/MBA, MD/MPH, or an MD/MS degree through one of three mission-based programs: the Health Education to Advance Leaders in Integrative Medicine (HEAL-IM), the Program in Medical Education for Leadership Education to Advance Diversity-African, Black and Caribbean (PRIME LEAD-ABC), and the Program in Medical Education for the Latino Community (PRIME-LC). The UCI School of Medicine is accredited by the Liaison Committee on Medical Accreditation and ranks among the top 50 nationwide for research. For more information, visit https://medschool.uci.edu/

About the University of California, Irvine: Founded in 1965, UCI is a member of the prestigious Association of American Universities and is ranked among the nation’s top 10 public universities by U.S. News & World Report. The campus has produced five Nobel laureates and is known for its academic achievement, premier research, innovation and anteater mascot. Led by Chancellor Howard Gillman, UCI has more than 36,000 students and offers 224 degree programs. It’s located in one of the world’s safest and most economically vibrant communities and is Orange County’s second-largest employer, contributing $7 billion annually to the local economy and $8 billion statewide. For more on UCI, visit www.uci.edu.

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