Are Pediatric GLP-1 Prescriptions Moving Faster Than the Evidence?

The rapid rise of glucagon-like peptide-1 (GLP-1) receptor agonists has transformed the treatment of obesity. Medications such as semaglutide (Wegovy), tirzepatide (Zepbound and Mounjaro), and liraglutide (Saxenda) have demonstrated an ability to produce significant weight loss in adults, making them some of the most consequential pharmaceutical developments in obesity medicine in decades. Increasingly, however, these medications are being prescribed to children and adolescents.

That expansion raises important questions. How strong is the long-term safety evidence in developing children? What are the potential consequences of altering appetite, digestion, body composition, and other physiological systems during childhood? And are medications being used to manage childhood obesity without adequately addressing the environmental and lifestyle factors contributing to it?

These questions deserve careful consideration as GLP-1 medications become a larger part of pediatric medicine.

In January 2023, the American Academy of Pediatrics published its Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity. The recommendations represented a significant shift toward more intensive treatment of childhood obesity. The guideline supported consideration of pharmacotherapy in pediatric patients, including off-label treatment in some younger children, while also recommending evaluation for bariatric surgery for certain adolescents beginning at age 13.

Its release also came shortly after the FDA expanded approval of GLP-1 therapy for adolescents. Questions about potential conflicts of interest subsequently emerged.

According to a July 2025 BMJ investigation, GLP-1 drug manufacturers provided approximately $2 million in corporate sponsorship to the AAP between 2012 and 2024. Investigators also identified pharmaceutical-industry payments to 10 of the 27 members of the guideline-writing committee and 17 of 77 members of the organization’s national leadership.

Those financial relationships were reportedly not disclosed within the guideline or its accompanying technical report. Financial relationships do not by themselves demonstrate that a clinical recommendation is incorrect. They do, however, make transparency particularly important when recommendations could substantially increase medication use among children.

Since the release of the guidelines, prescribing has increased substantially. The figures include:

• A 38% increase in pediatric GLP-1 prescriptions during the first year following the guideline.
• A reported 700% increase for two particular GLP-1 medications.
• CDC data showing approximately a 300% increase in adolescent obesity-medication prescribing between 2020 and 2023.
• Semaglutide accounting for approximately 57% of adolescent obesity prescriptions, with the majority going to adolescents with severe obesity.

Although only a small percentage of adolescents with obesity currently receive these medications, the speed at which prescribing is increasing makes the quality and duration of pediatric safety evidence increasingly important.

GLP-1 receptors are not confined to the digestive system. They are found throughout the body, including in the cardiovascular system. Clinical trials have documented small increases in heart rate among patients taking GLP-1 receptor agonists.

There is also a more indirect cardiovascular concern. Nausea, vomiting, and diarrhea — well-recognized side effects of GLP-1 drugs — can cause dehydration and significant electrolyte abnormalities. This may be especially relevant in younger patients because pediatric prescribing information for Mounjaro reports a higher incidence of vomiting and abdominal pain among children than adults.

One of the less frequently discussed issues surrounding GLP-1 medications is body composition. When a patient loses weight, not all of the lost weight comes from body fat. This issue may carry different implications for children than for adults.

Childhood and adolescence are critical periods for building muscle and achieving peak bone mass. Researchers therefore need to understand whether prolonged pharmacologically-induced weight loss could affect skeletal development, muscle development, or long-term body composition.

There is also the issue of what happens when treatment ends. Loss of metabolically active lean tissue may be one of several factors contributing to weight regain after discontinuation, potentially making GLP-1 therapy a long-term treatment rather than a temporary intervention.

Perhaps the largest unanswered question involves the widespread distribution of GLP-1 receptors themselves. They are found in the brain, gastrointestinal tract, pancreas, heart, kidneys, lungs, thyroid, blood vessels, adipose tissue, immune cells, and bone. Researchers continue to investigate exactly what those receptors do in each organ system and how prolonged pharmacological activation may affect them.

Interest in GLP-1 medications as potential treatments for conditions such as neurodegenerative disease further demonstrates that their biological effects extend well beyond blood-sugar control and appetite regulation. That does not mean these additional effects are necessarily harmful. It means that the biological picture is more complex than appetite suppression alone — and that long-term pediatric research is especially important.

The duration and size of existing pediatric trials remain significant limitations. The pediatric approval of Mounjaro for type 2 diabetes relied on a 30-week study involving 99 pediatric participants. The longest pediatric weight-loss study referenced lasted 68 weeks. Neither timeframe can establish what may happen over many years of treatment with respect to growth, puberty, bone density, neurodevelopment, reproductive development, or other long-term outcomes.

The debate surrounding pediatric GLP-1 prescribing ultimately involves a larger question: What is driving childhood obesity in the first place?

Childhood obesity develops within a complicated environment involving food quality and availability, highly processed diets, refined carbohydrates, sedentary behavior, screen time, sleep, socioeconomic conditions, genetics, family habits, environmental exposures, and numerous other influences.

GLP-1 drugs may help reduce appetite and body weight, but they do not directly change that broader environment. That distinction matters.

For some children and adolescents with severe obesity or related metabolic disease, pharmacotherapy may ultimately prove to have an appropriate place alongside nutrition, physical activity, behavioral care, family support, and treatment of related medical conditions. But medication should not prevent clinicians, families, researchers, or policymakers from confronting the circumstances contributing to the rise in childhood obesity.

The central concern surrounding pediatric GLP-1 prescribing is not whether these medications can produce weight loss. The available evidence shows that they can. The larger question is whether enough is known about what prolonged treatment does to a developing body.

Children are not simply smaller adults. Their bones are developing. Their muscles are growing. Their endocrine systems are changing. Their brains and reproductive systems are maturing.

Let’s close with the words of the pediatrician and the author of the article we’ve used as one of the sources for this post, Dr. Michelle Perro:

Underlying this is a more fundamental question. Childhood obesity is a symptom of an altered food environment: ultra-processed foods, GMOs and their associated pesticides, refined carbohydrates, seed oils, endocrine-disrupting chemicals, and a sedentary, screen-based childhood. Pharmacologic appetite suppression addresses none of these. It intervenes downstream of the pathology while leaving the causes intact.

A therapeutic approach that treats the symptom while ignoring the etiology and that commits a child to indefinite medication without long-term safety data does not meet the standard of care to which pediatric patients are entitled.

Your responses and feedback are welcome!

Source: “GLP-1 Receptor Agonists in Pediatric Patients: An Evidence Review and Cautionary Analysis,” GMOScience.org, 8/27/26
Source: “Clinical Practice Guideline for the Evaluation and Treatment of Children and Adolescents With Obesity,” Pediatrics, 1/3/23
Image by Gustavo Fring/Pexels

Is Obesity Reversible?

Obesity may affect the body differently at age 15 than it does at age 45. New research from Duke University School of Medicine suggests that adolescents retain a level of metabolic flexibility that is largely diminished by adulthood.

The study, published in the Journal of Clinical Investigation, found that although teenagers with obesity show early biological signs associated with metabolic disease, their bodies may still be able to adapt to the strain of excess weight. This resilience could make adolescence an especially important time for treatment.

By demonstrating that the biology of obesity changes with age, the findings point to a potential window in which obesity-related metabolic damage may be slowed, prevented, or possibly reversed before it becomes deeply established. John Rawls, Ph.D., a professor of molecular genetics and microbiology and member of the Duke Microbiome Center, said:

For a long time, medicine has tended to treat adolescents as little adults… But teenagers are still growing, building muscle and bone, and using energy in ways that are very different from adults. We wanted to understand how those differences shape obesity.

Why this research matters

Nearly one in five children in the United States has obesity. Without effective intervention, most children with obesity will continue to have obesity as adults, according to study co-author Sarah Armstrong, M.D., a pediatrician and medical weight management specialist at Duke Health.

The transition from adolescence to adulthood does not occur at exactly the same time for everyone. It generally takes place during the late teenage years and early 20s for women and during the early to mid-20s for men.

Researchers are now looking more closely at when the long-term health effects of obesity become biologically embedded. Understanding that timeline could help healthcare providers identify when treatment is most likely to alter a young person’s future health.

Teenagers’ gut microbiomes behave differently

The Duke research team examined two biological systems frequently connected to obesity: the microbiome and the metabolome. The gut microbiome is the community of bacteria and other microorganisms living within the digestive tract. The metabolome includes the chemicals produced as the body and its microbes break down food, generate energy, and carry out other essential processes.

Researchers first analyzed gut microbes collected from 287 teenagers participating in the Pediatric Obesity Microbiome and Metabolism Study. They confirmed that the microbiomes of adolescents with obesity differed in composition from those of teenagers at a healthy weight.

Jessica McCann, Ph.D., a senior research associate in molecular genetics and microbiology, then transplanted microbiome samples from adolescents with and without obesity into germ-free mice. In adult obesity research, transferring gut microbes associated with obesity can sometimes cause recipient mice to gain additional weight. That did not happen when the Duke researchers used microbiota collected from teenagers with obesity.

The result suggests that obesity-related changes in the microbiome are already beginning during adolescence, but those microbes may not yet be contributing to disease in the same way they often do in adults. Dr. McCann said:

This suggests there’s a developmental window in which the microbiome becomes involved in obesity… The relationship between the host and the microbiome may still be developing during adolescence, which means there may be an opportunity to change its trajectory.

In other words, the adolescent microbiome may be changing, but its relationship with the rest of the body has not necessarily become fixed. That could leave room for treatments that influence the microbiome before harmful patterns become more firmly established.

Early warning signs

Working with the Duke Molecular Physiology Institute, the research team also investigated how adolescents process nutrients. Adults with obesity frequently have elevated levels of branched-chain amino acids. They may also have higher levels of related substances called branched-chain keto acids, or BCKAs. Elevated BCKAs have been linked to insulin resistance and type 2 diabetes.

The adolescents in the Duke study displayed a different metabolic pattern. Their branched-chain amino acid levels were elevated, but their BCKA levels remained comparatively low.

The elevated amino acids may represent an early warning sign. However, the relatively low BCKA levels suggest that the teenagers’ bodies were still adapting to the metabolic pressure associated with excess weight. According to Dr. McCann,

The metabolome is showing early signs of disease progression, but it’s also showing evidence of adaptive plasticity.

This adaptive plasticity may help explain why obesity during adolescence is not biologically identical to obesity in adulthood. Teenagers’ bodies are still developing and may remain more capable of adjusting how they use and process nutrients.

A critical opportunity for obesity treatment

The findings strengthen the case for addressing obesity early rather than waiting until adulthood or until related conditions, such as insulin resistance, have fully developed. “The evidence increasingly supports intervening as early as possible,” said Dr. Armstrong, a professor of pediatrics at Duke.

During this period of metabolic flexibility, adolescents may be more responsive to weight-management strategies involving nutrition, physical activity, medication, or future microbiome-based therapies. The research does not suggest that one treatment will work for every teenager. Instead, it highlights the possibility that timing and individual biology may influence which approaches are most effective.

The study also challenges the idea that adolescent obesity should simply be managed using adult treatment models. Early biological warning signs do not necessarily mean that long-term metabolic disease is inevitable. By recognizing adolescence as a unique developmental stage, healthcare providers may have an important opportunity to intervene before temporary metabolic strain becomes a lasting health burden.

Your responses and feedback are welcome!

Source: “Study finds that obesity in adolescence may be more reversible than previously thought,” MedicalXPress, 8/24/26
Source: “Branched chain amino acid metabolism and microbiome in adolescents with obesity during weight loss therapy,” JCI, 7/15/26
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Opposite Signals Both Promote Weight Loss

Scientists have solved a puzzling question about a brain receptor involved in appetite: How can activating it and blocking it both lead to weight loss? The answer appears to depend on location.

In a study involving mice, researchers at the University of Cambridge found that drugs targeting the glucose-dependent insulinotropic polypeptide receptor, or GIPR, can influence body weight through separate regions of the brain. Activating the receptor in the brainstem reduced appetite, while blocking it in the hypothalamus strengthened the brain’s response to signals of fullness.

The findings, published in Nature Metabolism, could help explain why obesity medicines with seemingly contradictory mechanisms can produce similar outcomes. They may also point toward more effective combinations of GIPR-targeting treatments and drugs that act on the GLP-1 receptor, the target of medicines such as Wegovy and Ozempic.

As we know, substantial and sustained weight loss is often difficult to achieve through changes in diet and physical activity alone. Newer obesity medications work partly by influencing the biological systems that control hunger, fullness, and blood sugar.

Wegovy and Ozempic, for example, activate the glucagon-like peptide 1 receptor, commonly known as GLP-1R. Other treatments act on GLP-1R and GIPR at the same time.

That is where the scientific puzzle begins. Mounjaro and Zepbound activate GIPR as part of their mechanism. MariTide, an investigational medicine in phase 3 clinical trials, takes the opposite approach by blocking GIPR while activating GLP-1R. Both strategies can support weight loss, even though one turns the GIP receptor on and the other prevents it from working.

The Cambridge research suggests these approaches are not producing the same effect in the same place. Instead, they appear to engage distinct brain circuits that ultimately lead to reduced food intake and body weight.

To investigate, the researchers used genetically engineered mice in which GIPR had been removed from selected parts of the brain. Some mice lacked the receptor in the brainstem, an area near the spinal cord that helps regulate appetite and nausea. Others lacked it in the hypothalamus, which plays a central role in hunger, energy balance, and body-weight regulation. A third group of mice had not been genetically modified and served as a control.

The animals received different combinations of three types of treatment: a GIPR agonist that activated the receptor, a GIPR antagonist that blocked it, and a GLP-1-based drug. The researchers then measured how much the mice ate, how their body weight and fat mass changed, how well they regulated blood sugar, and which parts of their brains became active.

By comparing the results among the three groups, the scientists were able to identify the brain regions required for each treatment to work.

The experiments indicated that GIPR agonists depend largely on the brainstem. When the receptor was activated in this area, the mice ate less and lost weight. But when GIPR had been removed from the brainstem, the appetite-reducing effect was weakened, suggesting that this region is a key site of action for drugs that stimulate the receptor.

This helps explain how medicines that activate both GIPR and GLP-1R can influence eating behavior. Their effects are not limited to the digestive system or the pancreas; they also involve neural circuits that help determine when an animal stops eating.

GIPR antagonists worked differently. Their weight-loss effects depended more heavily on the hypothalamus. In this part of the brain, GIPR appears to act like a “brake,” reducing the strength of fullness signals coming from the brainstem.

Blocking the receptor releases that brake. As a result, signals telling the brain that the body has had enough food may become more powerful.

This means that activating and blocking GIPR can each reduce eating, but they reach that outcome through different routes. Activation directly engages appetite-suppressing pathways in the brainstem, while antagonism appears to make the hypothalamus more receptive to signals of satiety. That distinction may also explain why both strategies can complement GLP-1 medicines.

The findings offer a clearer biological explanation for the design of MariTide, which combines GIPR antagonism with GLP-1R activation. Because the two components may act through separate but interacting circuits, combining them could potentially produce a greater effect than targeting either pathway alone.

The researchers also found signs that GIPR antagonism could strengthen the effects of medicines aimed at the amylin receptor, another emerging target for obesity treatment. If that finding translates beyond mice, blocking GIPR might eventually be used to enhance several different types of weight-loss drugs — not only GLP-1 therapies.

Dr. Jo Lewis, the study’s first author from the Institute of Metabolic Science at the University of Cambridge, said:

Understanding which brain circuits respond to these medications — and how they do so — could help us design better drugs that produce more weight loss with fewer side effects, and which might work in combination with other obesity medicines to even greater effect…

Our work also strengthens the idea that the brain is central to obesity treatment. Obesity drugs are not acting simply on the gut or pancreas. Instead, they have important effects on specific, identifiable brain circuits that regulate appetite and food intake.

The research provides a useful framework for understanding an apparent contradiction in obesity pharmacology. Drugs that activate GIPR and drugs that block it are not necessarily cancelling out the same biological process. They may be acting in different brain regions, on different circuits and at different stages of the body’s appetite response.

However, the work was conducted in mice. Further research will be needed to determine how closely the same mechanisms apply to humans and whether targeting these pathways in combination can reliably improve weight loss, blood sugar control, or tolerability in patients.

Even so, the results underline an important shift in the science of obesity treatment. The effects of these medicines cannot be understood solely by studying the gut, insulin production, or digestion. Their success may depend just as much on where — and how — they alter communication within the brain.

Your responses and feedback are welcome!

Source: “Scientists solve the mystery of a brain “switch” that can trigger weight loss in opposite ways,” ScienceDirect, 8/15/26
Source: “Distinct brain regions mediate regulation of food intake in response to GIPR agonism or antagonism,” Nature Metabolism, 7/24/26
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Stigma and Association

Not long ago, an academic paper with several authors examined the existence and relationship of two concepts: weight stigma and weight stigma by association. The subjects were members of “a large, community-based sample.”

One objective was to rate parents on how caring and helpful they were willing to be, along with a rating to indicate how well they succeeded in that effort. When the results were tallied, it appeared that both obese parents and non-obese ones care equally for their children, be they daughters or sons. Furthermore, obese and non-obese parents are equally caring.

But: Obese parents are less effective, and parents of obese children are less effective.

One conclusion drawn by the researchers is that “Parents of children with obesity may experience weight stigma by association, which could have direct consequences for the parents, the children, and the parent-child relationship.” And, no matter how much they themselves weigh, parents of obese kids are rated as less effective. According to the authors of the paper,

There was also an effect of weight stigma wherein parents with obesity were also rated as less effective and helpful than parents without obesity.

Who is doing all this evaluating, and based on what standards?

It comes as no surprise to learn that a lot depends on who performs the evaluations. People who believe that parents are strictly and solely to blame for a child’s obesity do not care if those parents are themselves bulky or slender. The amount of censure is the same. And apparently, when either the young folks or their parents are obese, critics really don’t care how brilliant or talented the obese children in question may be. There is plenty of disapproval to go around.

One unfortunate result is that parents who are blamed and shamed “may internalize the negative parenting evaluations and subject themselves to further self-blame…,” which of course is exactly what their critics hope they will do. Even when parents exert themselves to make sure their methods “align with professional pediatric recommendations,” if their kids are overweight, those parents are still disrespected. The authors write,

One study found that parents who were stigmatized for their own weight reported greater use of restrictive feeding practices…

And yet, other research shows that when moms get strict about feeding, their kids are likely to eat more, not less. In effect, when an obese mama is picked on by someone who likes to stigmatize others, her kids will be even less carefully fed, and probably gain weight.

Another study dug deep and learned that when a girl is called “too fat” by a relative, her odds of being obese 10 years later increase by 62%. So maybe everyone should just pause and consider the many virtues of silence.

Several strengths

Characterized by its authors as possessing several strengths, this study is described as “the first randomized experiment to test weight stigma by association in a parent-child dyad using a large community sample.” Elaborate randomization standards are said to balance all potential variables and confounds across groups. It also involved large numbers of participants.

The authors note that their experimental stimuli “represented positive parenting practices” and
“used the same vignette of the parent-child dyad in all experimental conditions, which was crafted using the AAP parenting recommendations.” Summing up, they say,

Overall, the present randomized experimental study provides causal (rather than merely associative) evidence that weight stigma by association indeed occurs… Though a nascent area of research, weight stigma by association may have potential implications for parenting and effective pediatric obesity care.

Your responses and feedback are welcome!

Source: “Weight Stigma by Association Among Parents of Children with Obesity: A Randomized Trial,” ScienceDirect.com, 2022
Image by Tama66/Pixabay

Yale Study: Hunger Neurons in Weight Loss

For years, scientists believed that a group of brain cells known as agouti-related peptide, or AgRP, neurons played a straightforward role in metabolism: They stimulated hunger and resisted weight loss.

New research from Yale suggests the story is far more complicated.

In a study published in the Proceedings of the National Academy of Sciences (PNAS), researchers found that semaglutide, the active ingredient in Ozempic and other GLP-1 medications, appears to activate AgRP neurons rather than suppress them. Even more surprisingly, the study indicates that these hunger-promoting neurons may be necessary for maintaining the fat loss produced by the medication.

The findings challenge a long-standing assumption about the brain’s hunger circuitry and may help explain why newer GLP-1 therapies generate more substantial and lasting results than earlier weight-loss drugs.

Mateus d’Ávila, a Ph.D. candidate in neuroscience working in Tamas Horvath’s lab in the Department of Comparative Medicine at Yale School of Medicine (YSM) and first author of the study, said:

This completely changes how we think about the mechanism involved in these medications and provides new insight into the biology underlying their long-term effects, opening an avenue for the development of more efficient drugs.

The arrival of Ozempic and related GLP-1 therapies changed expectations, with some patients achieving sustained reductions of 10% to 15% of their body weight or more. Scientists know that these medications can reduce appetite and food intake. But appetite suppression alone may not fully account for their effectiveness.

Previous generations of weight-loss drugs could also substantially reduce hunger, yet they did not consistently produce the same degree of lasting weight loss as seen with semaglutide. That difference led the Yale team to suspect that GLP-1 medications were affecting additional biological systems.

One prominent theory held that the drugs worked partly by reducing the activity of AgRP neurons. Located in the brain’s hypothalamus, these neurons are strongly associated with hunger and feeding behavior. Because they encourage animals to seek and consume food, it seemed reasonable to assume that successful weight-loss treatments would need to inhibit them.

However, the role of AgRP neurons during long-term GLP-1 treatment had not been directly tested in a living organism. The Yale researchers set out to fill that gap.

Using a mouse model, the team combined several experimental approaches to examine what happened during semaglutide treatment. They tracked changes in body weight, food consumption, metabolism and energy expenditure.

The researchers also used genetic techniques to selectively remove or silence AgRP neurons. This allowed them to test whether the neurons merely responded to semaglutide or were actually required for the medication’s sustained effects.

The study results are striking. In mice genetically modified to lack AgRP neurons, GLP-1 treatment could initiate weight loss but could not sustain it. That suggested the neurons traditionally viewed as opponents of weight reduction were, in fact, helping preserve the drug’s long-term benefits.

Further investigations using electron microscopy, molecular biology and electrophysiology produced another unexpected finding: Semaglutide activated the AgRP neurons instead of inhibiting them. The researchers propose that this activation reflects the brain’s adaptation to the calorie deficit produced by GLP-1 treatment.

When calorie intake declines, AgRP neurons become more active as part of the body’s normal response to an energy shortage. Their best-known function is to increase hunger. The new study, however, suggests that their role is not limited to driving food intake. Under semaglutide treatment, the neurons may also participate in coordinating the loss of body fat.

In other words, the same neural system that signals a need for food may also help the body manage its energy stores during prolonged weight loss. This does not mean that hunger itself causes weight loss. Rather, it points to a previously unrecognized interaction between semaglutide, the brain’s response to calorie restriction, and the biological processes that determine whether lost weight stays off.

The discovery adds an important layer of complexity to scientists’ understanding of GLP-1 medications. Instead of simply shutting down the brain’s hunger signals, semaglutide may recruit parts of the hunger system and redirect their activity in ways that support sustained changes in body fat.

Because the study was conducted in mice, the results cannot yet be assumed to apply directly to humans. Researchers will need to determine whether the same neural mechanism operates in people taking semaglutide and other GLP-1 medications.

Still, identifying how the brain adapts during treatment could influence the next generation of obesity therapies. A more complete understanding of AgRP neurons might help scientists develop medications that preserve the benefits of GLP-1 drugs while improving their effectiveness, reducing unwanted effects, or helping a broader group of patients maintain weight loss.

d’Ávila said,

By identifying a previously unrecognized neural mechanism involved in sustaining weight loss, our work provides new biological insights that could eventually help researchers design therapies that are even more effective or have fewer side effects.

Your responses and feedback are welcome!

Source: “New study may change how we think about GLP-1s,” Yale News, 8/10/26
Source: “AgRP neurons are required for the weight-lowering effects of GLP-1 receptor agonists in female mice,” PNAS, 8/4/26
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