The high-profile semaglutide drugs Ozempic and Wegovy have changed how millions of adults manage type 2 diabetes and weight, respectively. Now many thousands of teenagers are being prescribed semaglutide and similar drugs in its class, raising questions about long-term consequences.
The drugs, which moderate blood glucose levels and create a sense of satiety, or fullness, were approved for teens aged 12 and up specifically for weight loss just a few years ago. Pediatricians are seeing striking health changes in their patients who are receiving the treatment, and many parents and their kids are eager to get the medication.
But some experts are uneasy about the trend and flag several concerns and uncertainties. The drugs are currently considered a lifelong treatment, which can be a difficult decision for adults but even more daunting for teenagers. Pediatricians and researchers have also called for long-term studies to address worries about the drugs’ effects on restrictive eating habits, bone strength, puberty and growth. This lack of longitudinal data gives health practitioners pause about teens’ future health.
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Weight and HealthThe relationship between weight, disease and health is complex and shaped by stigma as well as science. Research has shown having higher body fat increases the risk of certain health conditions such as diabetes and heart disease. But growing evidence suggests some people who may be heavy—such as those who are clinically classified as having obesity, according to their body mass index (BMI)—are metabolically healthy. The massive popularity of the new weight-loss drugs is set against this evolving understanding—researchers, clinicians and pediatricians are reevaluating how and when to manage weight.
“We’re not treating weight just to make kids smaller,” says Megan O. Bensignor, a pediatric endocrinologist and obesity medicine specialist at the University of Minnesota, who prescribes the drugs in her practice. “We’re trying to treat them to improve their long-term health.”
The new drugs are typically prescribed in the form of preportioned injector pens, which teens can administer at home themselves or with help from an adult. They work by activating the same signaling pathways as glucagon-like peptide 1, or GLP-1, a gut hormone that the body produces in response to food. The drugs, technically termed GLP-1 receptor agonists, help to kickstart the insulin-making process in the pancreas to bring down blood glucose levels. GLP-1 drugs also affect satiety centers in the brain, causing people to feel full faster—so they tend to eat smaller, less frequent meals. This can “help level set the playing field so it can be a little more achievable to engage in healthier behaviors around food,” says Aaron S. Kelly, co-director of the University of Minnesota’s Center for Pediatric Obesity Medicine.
“I don’t really crave chips or popcorn or things like that anymore,” says Jeremiah Jimenez, a 15-year-old in Texas who started the weight-loss drug Wegovy in March 2024. Jimenez says he’s always had a “bigger body” but rapidly gained weight during the pandemic. More concerningly his lab tests showed a fasting blood glucose level of 140, and he was diagnosed with prediabetes. He tried keto dieting and exercising but didn’t see substantial changes.
Small clinical trials on GLP-1 drugs in younger age groups have shown bigger reductions in weight and BMI compared with existing treatments and common lifestyle interventions such as exercise and diet. The results led the U.S. Food and Drug Administration to approve the daily-injected Saxenda (liraglutide) in 2020 and the weekly-injected Wegovy (semaglutide) in 2022. Both can be used as weight-loss treatments for children 12 and older. A JAMA study in May reported that more than 60,500 adolescents and young adults were prescribed a GLP-1 drug in 2023, a nearly 600 percent increase from 2020. “We suspect that this dramatic rise is likely related to weight management,” says Joyce Lee, a pediatrician and diabetes specialist at the University of Michigan, who led the study. While GLP-1 medications have been approved as treatments for children with type 2 diabetes since 2019, pediatric prescriptions spiked after Wegovy’s high-profile FDA approval for adolescents in December 2022, which specified that it can be used for weight loss.
“For over 20 years as pediatricians, we’ve been talking about ways that we can address obesity, and we have yet to find solutions to overcome it in some significant and substantive way,” Lee says.
Nearly 15 million children in the U.S have been diagnosed with obesity. The few medications traditionally prescribed for them are often minimally effective, and bariatric surgery is invasive and risky. Changes in diet and increased exercise, the most common treatment approaches, can be difficult to manage in children and adolescents. The new weight-loss drugs have created “a hope and optimism among my patients that I have frankly not seen before,” says Sarah C. Armstrong, a pediatrician and medical weight management specialist at Duke Health. But the drugs have also brought new challenges and concerns in navigating teens’ weight and health, she says.
“You’ve got this really dynamic [adolescent] period of four or five years—or maybe more really [because] the brain still develops in your mid-20s—where the impact of environmental factors is going to have lifelong consequences,” says Dan M. Cooper, a professor of pediatrics at the University of California, Irvine, School of Medicine. “If we’re going to use these drugs in adolescence, there’s got to be an organized attempt to really follow the long-term effects.”
Trials and EvidenceEvidence in children is not as robust as in adults, but a few clinical trials in younger age groups have tested GLP-1 drugs in combination with lifestyle modification counseling programs that included exercise and healthy eating. In 2020 a clinical trial of 251 kids aged 12 to 18 found liraglutide—an early-generation GLP-1 drug—cut BMI by at least 5 percent in most participants after 56 weeks. A 2022 trial of 201 teens aged 12 to 18 reported a higher treatment response from semaglutide: an about 16 percent BMI drop after 68 weeks.
“It varies by individual risk factors, but [researchers think] 5 percent BMI-weight change is probably starting to see clinical benefit,” Bensignor says. Children with obesity may see some metabolic changes, such as improvements in hypertension and lipid levels, she adds. Some data come from kids with so-called prediabetes, whose blood glucose levels are near the diabetic range. This research suggests that an 8 to 10 percent decrease in BMI may help with insulin resistance—that’s why semaglutide’s 16 percent BMI reduction is so appealing, Bensignor says.
The 2022 trial also showed that semaglutide helped to lower cholesterol and average blood glucose levels in children with and without diabetes. Other studies have backed up these findings, even most recently in kids as young as six to 12 years old—although the FDA has not approved any GLP-1 medications for weight loss in children under age 12. Side effects in teens were similar to those in adults, says Kelly, who was lead author of the 2020 liraglutide trial: the most common were nausea, vomiting and other gastrointestinal problems. Some studies have linked GLP-1 drugs to a small increased risk of gastroparesis, or gut paralysis, which impairs stomach emptying and digestion. Adverse effects caused about 10 percent of participants in the 2020 trial who received the once-daily liraglutide to stop treatment, while participants who received the once-weekly semaglutide in the 2022 trial had lower discontinuation rates of less than 5 percent.
Treatment FactorsPediatricians have to carefully consider the needs of their teenage patient before prescribing GLP-1 drugs—not any teen who is overweight or who wants to lose a few pounds can receive these medications. “We very frequently get referrals to have that conversation about whether a child is a good candidate or not,” says Mary Ellen Vajravelu, a pediatric endocrinologist at the University of Pittsburgh Medical Center. “It depends a lot on their other health complications.” The American Academy of Pediatrics’ (AAP’s) 2023 guidelines on obesity recommended GLP-1 drugs for children with high BMI or health conditions related to excess weight, such as prediabetes, type 2 diabetes, insulin resistance and fatty liver disease. Armstrong, a co-author of the AAP guidelines, notes that kids should first be screened for existing severe gastrointestinal issues or family history of thyroid cancer—some studies suggest a slight risk increase associated with GLP-1 drugs.
Finding an effective but tolerable dose varies tremendously among individuals, and GLP-1 drug prescriptions are incrementally increased over time to help people adjust. “The higher the dose, the more effective it is for weight but also the greater the proportion of patients who have symptoms like nausea or vomiting,” Lee says. “Some of my patients had to stop the medication because they can’t tolerate it, or we will have to just stop where they are at a level that they can tolerate.”
Grace, a Connecticut-based 13-year-old, uses relatively low amounts of semaglutide for her insulin resistance and weight loss—and for the medication’s anecdotal mental health benefits. “Because of her age, we started her at 0.125 [milligram],” says Jennifer, Grace’s mother. “Now she’s currently at 0.5.” (Their last names have been withheld for privacy.)
Armstrong and Bensignor say it’s important to closely watch a child’s health and weight throughout treatment to make sure they aren’t losing too much too quickly—and that their eating patterns aren’t becoming overly restrictive. Sometimes lowering the dose restores a child’s lagging appetite, Armstrong says, but she adds that behavioral psychologists should be consulted about any signs of an eating disorder. Researchers don’t know if GLP-1 drugs increase the risk of this, but experts agree further investigations are needed.
Long-Term UnknownsThese drugs’ dramatic effect on food intake—and potentially on nutrition—is one of the main reasons physicians hesitate about using them in teens. Little is known about long-term effects or how the drugs may influence a child’s future growth and development. Studies in teens have only lasted a few years at most.
“We know that the balance between nutrition and physical activity not only affects the child at that point but for the rest of his or her life,” says Cooper, who led a report on concerns over long-term GLP-1 use in younger populations. Poor nutrition and exercise in adolescents are known to affect muscle mass and bone mineralization (which help to increase bone strength and density), Cooper explains. He worries that the potential imbalance in calories and energy from the weight-loss drugs might lead to future bone fractures or osteoporosis. Similar concerns have been raised about the drugs influencing teenagers’ height and progression of puberty.
A spokesperson for Novo Nordisk, the company that makes Wegovy and Ozempic (a brand of semaglutide that is used to treat diabetes), says that “semaglutide did not appear to affect growth or pubertal development during the [2022] trial period…. We monitor the safety profile of our products and collaborate closely with regulatory authorities to ensure patient safety, including in children and adolescents.”
Cooper says that clinicians and researchers should track teens on GLP-1 drugs as they age and should precisely measure how much they lose in fat, lean tissue or bone mass. He acknowledges that GLP-1 drugs might help in very specific cases, such as teens with obesity and a high risk of type 2 diabetes or heart disease. “To not treat the child when you have a drug that would help them would be an error,” Cooper says. But medication can only be part of the path forward: “We have this population of children, particularly low-socioeconomic kids, that find themselves in an environment where they become obese, where they don’t have enough physical activity and they don’t have access to enough healthy food,” he says. “That’s a social and medical problem, and we have to pay as much attention to that as we do to creating new drugs.”
Vajravelu, Bensignor and Armstrong all say GLP-1 medications shouldn’t completely replace healthy lifestyle changes such as better physical activity, nutrition and sleep. Jimenez, for instance, follows an “80-20” rule with meals—eating more lean proteins such as grilled chicken and high-fiber fruits and vegetables but still leaving room for things like pizza and ice cream. He also sticks to a regular workout schedule: an hour of cardio three days a week and 30 minutes of weight lifting with a personal coach on another three days. These kinds of changes need to be part of any weight-loss treatment, and kids taking a GLP-1 drug may need support from a variety of experts such as dietitians, social workers and food education specialists.
“I don’t want people to think that this is literally the easiest thing in the world, like we’re taking the easy way out,” Jimenez says. “It is very hard to get up and go work out and to not eat [junk food] and put it down and to portion control because you’re so used to it.”
Future ConsiderationsStudies suggest most people who start a GLP-1 treatment will need to stay on it indefinitely. The clinical trials showed that children regained weight after stopping treatment. Kelly and his team are now designing studies to understand if teens can reduce the dose over time—or even stop taking the drug entirely. “The human body is exceedingly complex, and everybody’s wired differently,” he says. He hopes his future studies can further explore whether some people could briefly use a GLP-1 treatment and “somehow have their physiology reset.” Several past studies suggest that “if you’re obese as an adolescent, then you’re likely to remain obese as an adult,” Lee says. A GLP-1 drug might get kids on a “better trajectory” with their weight—but it’s still too early to tell, she says.
Two studies in 2023 found that semaglutide was not a cost-effective long-term option for adolescents. Accessibility and high costs of these drugs (approximately $1,000 a month) are huge barriers for adults, and more troubling for teens, who may experience coverage changes as they get older, Vajravelu says. “It’s hard to prescribe a medication in childhood that we think you’ll need for decades—and especially because it’s likely that the medication access will be interrupted for all sorts of reasons, including insurance changes and supply issues,” she says. And Kelly wonders how interrupted access might affect someone during their vulnerable teenage years. “That is a scenario that we need to look very carefully at because we’re putting that individual in a place where they may feel some desperation to try to lose that weight again without the medication,” he says.
Grace’s mother, Jennifer, faced access hurdles with her daughter’s prescription and ultimately had to turn to a cheaper option: compounded semaglutide. Compounded medications are versions of a drug made by compounding pharmacies rather than the developer when it is under shortage. The FDA recently warned of compounded semaglutide’s overdosing risks. Jeremiah Jimenez’s mother, Suzie Jimenez, who had used Wegovy herself and now takes a similar medication called Zepbound, can afford their prescriptions through her employer’s insurance. But she says that if that situation changed, “I would find a way to prioritize [the drug] and make it part of our budget because it is a lifelong medication and it seems to be working very effectively for both of us.”
Beyond reductions in BMI, Bensignor says GLP-1 drugs seem to affect some people’s quality of life. “My patients are feeling better in general. They can move better; they feel more comfortable in their bodies,” she says. “I think this is just another validation that it’s not their fault, that obesity has biological underpinnings.”
Source : Scientific American