Semaglutide Trials Show Promising Results

GLP-1 medications have transformed obesity treatment for many adults and adolescents. Now, new research suggests these drugs may also benefit younger children with obesity — even as their rapidly increasing use raises important questions about safety, access, and long-term care.

Results from Novo Nordisk’s late-stage STEP Young trial found that 40.4% of children ages 6 to younger than 12 who received semaglutide were no longer classified as having obesity after 68 weeks, assuming they fully followed the prescribed treatment.

Semaglutide is the active ingredient in Wegovy, a once-weekly injectable medication used for chronic weight management. Wegovy is currently approved in the United States for adults and adolescents ages 12 and older with obesity, but not for children younger than 12.

The STEP Young trial compared once-weekly semaglutide injections with a placebo. Every participant also received lifestyle support throughout the study, including guidance on a reduced-calorie diet and increased physical activity.

According to Novo Nordisk, the trial met its primary goal by demonstrating a greater reduction in body mass index, or BMI, after 68 weeks among children receiving semaglutide compared with those receiving a placebo.

Martin Holst Lange, Novo Nordisk’s chief scientific officer, said:

We are encouraged by the positive STEP Young results and semaglutide’s potential to help children living with obesity who need medical treatment, alongside lifestyle changes, to better manage their obesity.

The company also reported that semaglutide’s overall safety and tolerability were consistent with findings from clinical trials involving adolescents and adults. However, additional study details and longer-term monitoring will be important for understanding how treatment may affect children as they grow and develop.

The trial results arrive as GLP-1 use among children younger than 12 is already increasing in the United States. A separate study led by researchers at NYU Langone Health found that GLP-1 prescribing among children ages 8 to 11 with obesity and without diabetes was 310 times higher in June 2026 than when prescribing began in 2019. More than 20,000 children in this age group received GLP-1 prescriptions during the study period. The study results were published in Pediatrics earlier this month.

Despite that rapid growth, the overall percentage of young children receiving these medications remains low. Prescriptions are still less common among children ages 8 to 11 than among adolescents ages 12 to 17.

Lead investigator Babak J. Orandi, M.D., Ph.D., said:

Our study offers the first national overview in young children of the use of GLP-1 drugs to fight the obesity epidemic in the United States and shows that while the absolute numbers of children under the age of 12 receiving GLP-1 treatment is still low, GLP-1 use is accelerating rapidly.

Researchers examined electronic health records from Epic Cosmos, a national database containing information from more than 300 million patients across thousands of hospitals and health clinics.

Nearly 94% of the young children prescribed GLP-1 medications had severe obesity. Approximately 65% also had at least one obesity-related health condition, such as high blood pressure, elevated cholesterol, or sleep apnea. About one-quarter had prediabetes.

These findings suggest that physicians have generally been prescribing the medications to children facing significant health risks rather than using them as a routine weight-loss intervention.

GLP-1 medications can support weight loss by reducing appetite, slowing digestion and improving blood sugar regulation. For children with severe obesity, treatment may also help reduce the likelihood of developing diabetes, liver disease, cardiovascular problems and other chronic conditions later in life.

Dr. Orandi described careful GLP-1 use as “a valuable tool in confronting the obesity epidemic among young Americans.” He also emphasized the need to monitor treated children over time to ensure the medications remain safe and effective.

The NYU Langone study also identified a potential socioeconomic divide. Young children with obesity living in higher-income communities were 55% more likely to receive GLP-1 medications than children living elsewhere.

The medications can be costly, and insurance coverage varies considerably. Families with stronger insurance benefits, greater financial resources or easier access to pediatric specialists may therefore be better positioned to obtain treatment.

Co-senior author Allan B. Massie, Ph.D., said,

Physicians and health policymakers alike have a responsibility to ensure, as use of GLP-1 medications continues to rise, that all young children with obesity who need these drugs have access to them.

Addressing this disparity will become increasingly important if clinical trials support expanding GLP-1 approvals to younger age groups.

The STEP Young results are promising, but they do not mean semaglutide is appropriate for every child with obesity. Treatment decisions should consider the child’s overall health, obesity severity, related medical conditions, developmental needs, and family circumstances.

Medication is also not presented as a replacement for nutrition, physical activity, or ongoing medical care. In the STEP Young trial, semaglutide was used alongside structured lifestyle changes.

Further research will be needed to answer several key questions, including how long children may need treatment, whether weight returns after medication is discontinued, and how extended use could affect growth, development, and long-term health.

For now, the two studies point to a rapidly evolving area of pediatric medicine. GLP-1 medications may eventually offer an important option for younger children with severe obesity, but their growing use will require careful prescribing, long-term monitoring, and equitable access to qualified medical care.

Your responses and feedback are welcome!

Source: “Novo Nordisk says semaglutide cut obesity rates in young children in trial,” Reuters, 9/7/26
Source: “Novo Nordisk STEP Young phase 3 data: 40.4% of children living with obesity achieved a BMI below the obesity threshold with semaglutide and lifestyle modification,” GlobeNewswire, 9/7/26
Source: “GLP-1 Use Among Young Children With Obesity in US Remains Rare but Is Rising Rapidly,” NYU Langone Health, 9/4/26
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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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