Pediatric Research Update: Anti‐Obesity Medication in the Management of Children and Adolescents With Obesity

Article Summary

Pediatric obesity is a global public health concern, with less than 15% of youth with obesity managing to lose their excess adiposity in adulthood. Health behavior and lifestyle treatment remains the recommended first-line approach, but newer anti-obesity medications offer an additional treatment option, positioned between behavioral management and higher-efficacy surgical interventions. Long-term effectiveness and safety data are still limited.

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Article Review

This review highlights the 2023 AAP clinical practice guideline, which shifts obesity treatment from a stepwise process to using the full spectrum of options as appropriate. Health behavior and lifestyle treatment (HBLT) has a good safety profile but limited effect on weight (BMI decrease of 1.18 kg/m2). Metabolic and bariatric surgery is far more effective, with BMI decreasing on average 13.09 kg/m2 for sleeve gastrectomy, though long-term safety still needs careful consideration. The AAP guidelines recommend offering bariatric surgery to adolescents 13 and older with severe obesity.

For monogenic forms of obesity, two phase 3 trials of setmelanotide (a selective MC4 receptor agonist) reduced hunger and weight in patients with syndromic obesity due to POMC, PCSK1, or LEPR deficiency: 80% of the POMC group and 45% of the LEPR group lost at least 10% of body weight. In Bardet-Biedl syndrome, 32.3% of patients over 12 achieved the same. Common side effects were headache, gastrointestinal upset, and skin hyperpigmentation. Setmelanotide was FDA-approved in 2020 for POMC, PCSK1, and LEPR deficiency, with approval for Bardet-Biedl following shortly after as a separate indication. Metreleptin, approved for lipodystrophy since 2014, has also been used in patients with congenital dysfunctional or biologically inactive leptin variants from LEP gene changes.

For polygenic obesity, a 2016 Cochrane review covered 21 RCTs total: metformin (11), sibutramine (6), and orlistat (4), showing a mean BMI reduction of 1.3 kg/m2. Sibutramine was later withdrawn for safety concerns; metformin was never approved for obesity, leaving orlistat as the only approved option at the time. An update to that review added metformin, topiramate, phentermine/topiramate, exenatide, liraglutide, and semaglutide, showing a BMI reduction of 1.71 kg/m2, ranging from 0.8 to 5.9 units depending on the drug. Today, the FDA has approved four AOMs for chronic pediatric weight management: orlistat, liraglutide, semaglutide, and phentermine/topiramate. Response varies widely across patients. Trials are underway to extend these options to children 6 to 11, and tirzepatide is being studied from age 6 up.

Because obesity is a chronic disease, AOM use alongside lifestyle and behavioral treatment is likely indefinite, though clear guidance is still lacking. Treatment response tends to follow two phases: rapid BMI reduction, then a plateau tied to neuroendocrine hormonal adaptation. Long-term safety data from adults show gastrointestinal effects are most common, with a higher risk of bowel obstruction and gastroparesis in patients on GLP-1RAs compared to bupropion-naltrexone.

Paired with lifestyle changes, AOMs may help with portion control, though it is still unclear whether they help patients build healthier eating and activity habits long term. Screening for pre-existing nutritional risk is important to avoid malnutrition or disordered eating once treatment starts. In adults, resistance training combined with AOM treatment has helped with weight maintenance, but pediatric guidance is still lacking.

Cost and access remain major barriers, both for patients and for primary care clinicians trying to deliver this care. Adherence depends on ongoing engagement with patients and families, built on shared decision-making, motivational communication, and reducing weight stigma, an approach reflected in the 5As framework: ask, assess, advise, agree, assist. Long-term effects, including on brain development, mental health, and cancer risk, remain largely unknown, and predicting individual response to treatment is still difficult.

Discussion

This review supports starting obesity treatment at the time of diagnosis alongside lifestyle intervention, rather than following a step-wise approach. Current pharmacotherapy is effective to varying degrees, but more research is needed on long-term efficacy and safety. A clearer definition of adequate versus suboptimal weight loss would help clinicians guide patients more confidently. For some patients, current interventions won't be enough, and additional treatment options will be needed. As pharmacotherapy for adults continues to advance, pediatric studies of similar interventions are likely to follow, and evidence on how best to combine AOMs with HBLT in adolescents remains a key need.