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Authors of a literature review in provide clinical guidance regarding various interventions -- most notably pharmacotherapies -- for obesity in youth.

Scientists reviewed about a dozen drugs. Orlistat, liraglutide, phentermine, and an extended-release combination of phentermine with topiramate are approved by the FDA for treating obesity in adolescents. Additionally, setmelanotide can be effective, but is used only for people with specific genetic disorders. The other medications analyzed in the review are used off-label for weight loss, with metformin being a classic example.

Co-author Joan C. Han, MD, is chief of pediatric endocrinology and diabetes with Icahn School of Medicine at Mount Sinai in New York. She discussed the review and its findings with the Reading Room. The exchange has been edited for length and clarity.

What key question was this review designed to address -- and why did you choose to pursue it?

Han: The goal of this review was to share information regarding the newest treatments for pediatric obesity. For many years, FDA approval for medications to treat obesity in youth has lagged behind the available options in adults.

Recently, however, several medications have had their approved age range lowered to 12 years old. Plus, a novel weight loss medication targeting specific genetic disorders leading to obesity due to deficits in the leptin signaling pathway -- a key regulator of appetite and body weight -- became available this year for children ages 6 years and older.

Would you summarize your key conclusion?

Han: Pharmacotherapy for adolescent obesity in the general population is safe and effective, and replacing specific deficits in children with genetic obesity disorders would be a successful precision medicine approach.

Are there off-label medications that may help address obesity but that some clinicians may not know about?

Han: In the past, many of the medications used to treat obesity in adults were being prescribed off-label to adolescents, often without health insurance coverage and with great hesitation and concern on the part of prescribers due to lack of an FDA indication in this younger age group. However, now that some of these medications have received FDA approval for teenagers, hopefully more youth with obesity will have access to these safe and effective therapies.

One medication that is sometimes prescribed off-label to children with obesity is metformin, which can produce modest improvements in weight and insulin resistance. However, in light of newer therapies, such as liraglutide and combination phentermine/topiramate, that induce greater weight loss and are FDA approved for ages 12 and older, we would recommend that prescribers consider these newer therapies when treating adolescent obesity.

With regard to setmelanotide -- a medication that targets the melanocortin-4 receptor (MC4R): it should only be used in children with disorders that affect the leptin signaling pathway upstream of the MC4R receptor.

Metreleptin is effective in children with obesity due to congenital leptin deficiency, an extremely rare disorder that is typically only observed in offspring of consanguineous parents. However, metreleptin is not FDA approved for this indication, so it is only available for off-label compassionate use for these patients in collaboration with the drug manufacturer.

Are there any therapies that show major promise and, as such, might merit a particularly robust research focus in the relatively near future?

Han: Semaglutide and tirzepatide are the medications to keep an eye on. Semaglutide is already approved for adult obesity, and based on the data thus far available in teens, we anticipate that this will be approved in adolescents.

Tirzepatide is currently only approved for type 2 diabetes in adults, but it shows tremendous promise for weight loss too. Therefore, we anticipate it to be another drug that may also soon be approved for treatment of obesity.

What do you see as the take-away messages for clinicians from this review?

Han: Improving nutrition and physical activity is the foundation for better health, but in individuals with obesity, lifestyle alone is often not enough to induce sufficient or sustained weight loss, especially for those who have severe obesity.

Pharmacotherapy can serve as an important adjunct to lifestyle modification. In the past, only orlistat was approved for long-term use in adolescents with obesity. Now we have two more therapies, liraglutide and combination phentermine/topiramate, to add to our armamentarium for adolescents. Plus, with more medications under development, health care providers can offer teens with obesity more intermediate steps before considering bariatric surgery.

It's important to note that also that, with the alarmingly high prevalence of childhood and adult obesity, which has become even worse during the COVID pandemic, pharmacotherapy for weight loss should be considered sooner and more widely by clinical prescribers.

Insurance providers should be encouraged to cover the cost of these medications because the long-term benefit of treating obesity and avoiding and reversing complications of obesity are ultimately a cost-savings to society and more importantly because of the well-being and longevity of the human population worldwide.

Clinical implications

• Pharmacotherapy for adolescent obesity in the general population is safe and effective.
• Newer therapies, such as liraglutide and combination phentermine/topiramate, are recommended for treating adolescent obesity.
• As childhood and adult obesity becomes more common, pharmacotherapy should be considered sooner and more widely.

Read the study here and expert commentary on the clinical implications here.