麻豆传媒

Adolescent obesity is not merely a cosmetic concern, but a medical threat especially in light of long-term cardiometabolic outcomes. In particular, it is associated with hypertension, dyslipidemia, diabetes mellitus, and premature mortality. Hence, it is essential for physicians to counsel patients and families on the importance of weight reduction early on.

An adolescent is diagnosed with obesity if the BMI is ≥95th percentile, and morbid obesity if the BMI is ≥120% of the 95th percentile or ≥35 kg/m². The goals of treatment in these patients are weight loss and weight stabilization, prevention of future adverse health outcomes, and improvement of quality of life.

As with obesity in adults, the initial management involves sustainable lifestyle changes that focus on caloric restriction and increased physical activity. Even so, the achievement and maintenance of weight loss by this approach is challenging. It is well established that the pathogenesis of weight gain and satiety are controlled by central and peripheral processes that may impede the ability to lose weight. Therefore, pharmacologic agents that can target these mechanisms may serve as adjuncts.

Anti-obesity medications may be part of the multimodal approach in managing this chronic condition. The 2017 Endocrine Society Guidelines suggest pharmacological treatment for adolescents if a formal lifestyle modification program fails to limit weight gain or to ameliorate comorbidities. However, the FDA-approved pharmacotherapy options for use in this population remain limited. This is mainly because only few medications have been studied among adolescents in randomized clinical trials. Consequently, this leads to the off-label use of certain weight loss medications approved only for adults.

A recently published review by Raman et al. in looks at approved and off-label drugs for the management of adolescent obesity. The authors discuss their efficacy, safety, and practical considerations. Data from clinical trials and observational studies are included.

Orlistat and liraglutide showed reductions in BMI, favoring intervention. However, their use is limited by unpleasant gastrointestinal side effects. Phentermine is approved for use among adolescents over 16, and its extended-release combination with topiramate may be used in those aged 12 years and older; however, it is important to highlight the teratogenic risk of the ER combination.

An association with obesity and the melanocortin pathway is well established. Setmelanotide was developed with a precision medicine approach, targeting the melanocortin-4 receptor (MC4R). The drug produced clinically significant reduction in both body weight and hyperphagia.

Studies on metformin use among adolescent patients with insulin resistance showed modest benefit in terms of weight loss; the medication is currently used off-label for this purpose. Bupropion has been used for depression, with weight loss noted as a side effect. However, caution is needed as it may increase the risk of suicidal ideation and other psychiatric disorders. Opiate antagonists, like naltrexone, have been observed to reverse hyperphagia and obesity but current evidence to support its use in adolescents is limited.

The review also explores emerging therapies still in development. For example, semaglutide, a GLP-1 receptor agonist, with demonstrated benefits among adults with obesity is currently being studied in a phase III clinical trial in adolescents (STEP TEENS study).

While ongoing clinical research efforts hold promise, more dedicated studies in the adolescent population are needed to promote the approval of regulatory agencies. We call for more clinical trials that will look into combinations of drugs to examine their synergistic effects, rates of adverse events and weight regain, and their long-term effects on the development of related comorbidities.

Diana Colleen M. Dimayuga, MD, is an endocrinology fellow at St. Luke's Medical Center Global City, Taguig, Philippines. Michael L. Villa, MD is the chair of the Department of Medicine at St. Luke's Medical Center Global City and is the Immediate Past President of the Philippine College of Endocrinology, Diabetes and Metabolism.

Read the study here and a Q&A with a study co-author here.