The Problem With Excluding Children From GLP-1 Trials In The U.S.

By Evan P. Nadler, MD, MBA, founder, ProCare Consultants and ProCare TeleHealth

Over 150 million Americans — approximately 40% — have obesity. Among children, the number is also staggering: 15 million. Most people understand that obesity increases the risk of Type 2 diabetes, cardiovascular disease, and sleep apnea, among other conditions, but few realize that these diseases are becoming more common in children. With most diseases, the longer you have it, the worse it gets. Obesity is no different. The damage is cumulative. It’s not just about how much you weigh — it’s about how long your body has been exposed to that weight. So one would think that the imperative to find solutions for childhood obesity would be front and center for those who are involved in clinical research involving the next generation of anti-obesity medicines. Unfortunately, that isn’t the case.

Anti-Obesity Drugs In Development, But Not For Children

Indeed, times are very exciting in the world of anti-obesity pharmacotherapy with the initial FDA approvals of the weekly injectable medications semaglutide and then tirzepatide to treat obesity. And now, semaglutide is available in a daily oral formulation. The company that makes tirzepatide is also pursuing an oral formulation of their own small molecule GLP-1 receptor agonist, orforglipron. There are a number of other anti-obesity medications in the drug development pipeline, including a monthly injection (maritide) and even a medication that stimulates three different receptors (retatrutide) that may be involved in obesity pathogenesis. This triple agonist has been shown to have weight loss outcomes similar to bariatric surgery in Phase 3 trials.

So you might ask why I’m writing this piece about childhood obesity then. Children are certainly included in the expanding world of anti-obesity medications and their development, right? Well, as mentioned above, that isn’t what’s happening. To date, there is only one GLP-1 agonist FDA-approved for use in children 12 and up, semaglutide.¹ Its predecessor, liraglutide, is also approved for ages 12 and up. However, the weight loss associated with liraglutide is far less than with semaglutide, and it requires a daily injection, which is undesirable for children.  Interestingly, there are data available for the use of liraglutide in patients with obesity as young as age 6 , but because its patent has expired,  the company has no intention of filing for FDA approval for children that age.²

There is more immediate hope with tirzepatide, which is currently being studied in patients ages 12 to 18. That trial is expected to be completed in 2027, but trials for children down to age 6 aren’t expected to be completed until 2030. Now, the FDA did approved tirzepatide for adults in November 2023, but that leaves at least a three- or four-year access gap between a person who is 18 years old and a person who is 17. Is there a medical difference between obesity in a 17-year-old and an 18-year-old? Obviously not.

The Issue With Excluding Children From Obesity Trials

The fundamental problem is that the FDA does not require children to be included in the initial clinical trials. They are encouraged but are not mandatory. Rather, the Pediatric Research Equity Act (PREA) requires pediatric studies for an investigational drug when the disease does not occur in children. What this means is that companies must submit a Pediatric Study Plan (PSP), but PREA allows them to defer those pediatric trials until the adult trials are complete and adult safety is established. Most companies understanding that there is far more profit to be made in the adult world defer the pediatric studies until later, explaining why there will be several years between tirzepatide being available for a 17-year-old as opposed to an 18-year-old with obesity.

In its most recent draft guidance, FDA’s 2025 Draft Guidance on Obesity‑Drug Development, pediatric populations are more explicitly addressed.³ It states that pediatric trials are expected for anti-obesity medications under development and provides some details regarding clinical trial expectations for these cohorts. It also suggests that the plans for the inclusion of children should be integrated early in the new drug development plans. However, this is still not a requirement, merely a suggestion. Wouldn’t it have made more sense for the oral semaglutide trials to have included children down to age 12 since the injectable formulation is already approved for that age? Why do children have to wait an additional three to four years for a new pediatric trial of oral semaglutide until they get the benefit of a daily pill that adults already have access to? It seems obvious that if the unique sodium N-(8-[2-hydroxybenzoyl]amino)caprylate (SNAC) technology is suitable for an 18-year-old, the same would be true for a 17-year-old. Again, the distinction is completely arbitrary and not based on scientific differences between these two ages. Maybe that’s why Europe handles things differently.

Why The Europeans Got It Right

The European Union (EU) requires that every new drug submitted for marketing authorization have a Pediatric Investigation Plan (PIP) under their Paediatric Regulation (Regulation (EC) No 1901/2006).⁴ Only  a waiver allows a pharmaceutical company to avoid this obligation,  and the PIP must be reviewed and agreed upon before the completion of the adult trials. Yes, the actual studies in children can be deferred until after the adult approval is given, but at least there is a legal mandate for an approved plan for children — not merely a suggestion as there is in the U.S. In practice, more pediatric drug development plans were agreed upon in the EU than in the U.S.⁵ It also makes better sense than the U.S. approach, since it is a legal mandate.

The Bottom Line For Treating Childhood Obesity

So what does this all mean for children with obesity in the U.S.? Despite all the GLP-1- development, children are not part of the gameplan. There is no PSP in the U.S. or PIP in the EU for retatrutide available in public regulatory databases. The same goes for maritide. Sadly, while the childhood obesity epidemic rages on, they won’t benefit from new medical breakthroughs any time soon. The time has come for the FDA to rethink how it approaches clinical trials in children for the sake of the 15 million children with obesity — and really for all children ignored by the current regulatory environment. There is no reason to continue to discriminate against this vulnerable population.

References:

1. Weghuber D, Barrett T, Barrientos-Pérez M, et al. Once-Weekly Semaglutide in Adolescents with Obesity. N Engl J Med. 2022 Dec 15;387(24):2245-2257.
2. Fox CK, Barrientos-Pérez M, Bomberg EM, et al. Liraglutide for Children 6 to <12 Years of Age with Obesity - A Randomized Trial. N Engl J Med. 2025 Feb 6;392(6):555-565.
3. https://www.fda.gov/media/71252/download
4. https://www.ema.europa.eu/en/human-regulatory-overview/paediatric-medicines-overview/paediatric-regulation
5. Christiansen H, De Bruin ML, Hallgreen CE. Mandatory requirements for pediatric drug development in the EU and the US for novel drugs-A comparative study. Front Med (Lausanne). 2022 Oct 31:9:1009432.

About The Author:

Evan P. Nadler, MD, served as co-director of the Children’s National Obesity Programs and director of the Child and Adolescent Weight Loss Surgery Program at Children’s National Hospital from 2009 until 2023. He was also a tenured associate professor of surgery and Pediatrics at The George Washington University School of Medicine & Health Sciences and continues there as an adjunct associate professor. His current pursuits include pediatric obesity treatment program development, authoring a book on obesity, and educating the public about obesity via his YouTube channel, website, and media appearances. Dr. Nadler is an international leader in the field of child and adolescent obesity, has authored multiple publications and textbook chapters on the topic of pediatric bariatric surgery, and was one of the founding members of the Childhood Obesity Committee of the American Pediatric Surgery Association.