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This article has not been peer reviewed but has been accepted for publication. It is the authors' manuscript version prior to publication in the Journal of Clinical Pharmacology.


Obesity is an ongoing global health concern and has only recently been recognized as a chronic disease of energy homeostasis and fuel partitioning. Obesity afflicts 17% of US children and adolescents. Severe obesity (³120% of the 95th percentile of BMI-for-age, or a BMI of ³35 kg/m2) is the fastest growing subgroup and now approaches 6% of all US youth. Health consequences (e.g., type 2 diabetes, coronary heart disease) are related in a dose-dependent manner to severity of obesity. Since therapeutic interventions are less effective in severe obesity, prevention is a high priority.

Treatment plans involving combinations of behavioral therapy, nutrition and exercise achieve limited success. Only one drug, orlistat, is FDA-approved for long-term obesity management in adolescents 12 years and older. As part of comprehensive medication management, clinicians should consider the propensity for a given drug to aggravate weight gain and to consider alternatives that minimize weight impact. Medication management must take into account developmental changes as well as pathophysiology of obesity and comorbidities.

Despite expanding insight into obesity pathophysiology, there are gaps in its translation to therapeutic application. The historical construct of obesity as simply a fat storage disorder is fundamentally inaccurate.

The approach to adjusting doses based solely on body size and extrapolating from therapeutic knowledge of adult obesity may be based on assumptions that are not fully substantiated. Classes of drugs commonly prescribed for comorbidities associated with obesity should be prioritized for clinical research evaluations aimed at optimizing dosing regimens in pediatric obesity.