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.
Their commentary appears as a perspective article in the Journal of Clinical and Translational Science. Its main author is Dan M. Cooper, a professor of pediatrics in the University of California, Irvine School of Medicine.
“These drugs administered without proper supervision could cause a minefield of health and emotional problems for children as they age.”
In the perspective, the team note 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,” says Cooper, associate director of the university’s Institute for Clinical and Translational Science and interim director of its 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 affect 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 point 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,” says Jan D. Hirsch, one of the coauthors and dean of the School of Pharmacy and Pharmaceutical Sciences at UC Irvine. “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 notes 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 affected marginalized groups 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,” says Emma Cooper, a resident physician in psychiatry and human behavior in the UC Irvine School of Medicine.
“As the rate of mental health disorders, including eating disorders, continues to rise, health care providers should be screening for and intervening on inappropriate use of these medications.”
Researchers believe appropriate pediatric health could also under threat, not only by the well documented rise of counterfeit drugs but also by illegitimate access through the internet.
The team outlines six calls to action. Targeting the National Institutes of Health network of academic centers that are recipients of Clinical and Translational Science Award hubs across the nation, the call-to-action includes:
- 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.
- 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.
- 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% of American school children.
- 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.
- 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.
- 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.
Source: UC Irvine