Pharmacotherapy of Childhood Obesity
An evidence-based, conceptual approach
- Michael Freemark, MD
- Division of Pediatric Endocrinology and Diabetes, Duke University Medical Center, Durham, North Carolina
- Address correspondence and reprint requests to Michael Freemark, MD, Box 3080, Duke University Medical Center, Durham, NC 27710. E-mail: freem001{at}mc.duke.edu
- AMPK, AMP-activated protein kinase
- DPP, Diabetes Prevention Program
- IGT, impaired glucose tolerance
- PCOS, polycystic ovary syndrome
This review provides a comparative analysis of the benefits of lifestyle intervention and pharmacotherapy in adults and children using previously published meta-analyses, as well as new data published within the past 2 years. The manuscript critically summarizes the potential risks of various established (orlistat, sibutramine, and metformin) and new (rimonabant) pharmacologic agents and presents a conceptual approach to selection of patients for pharmacotherapy, tailored drug selection, and timing of intervention.
Perils and promise of pharmacotherapy
Forty-five years after an amphetamine was approved for the treatment of obesity in adults, an expert in the field characterized a new therapeutic formulation as being effective and long-lasting, posing “little risk” (1). Four years later, others (2) “confirmed the weight-reducing efficacy and good tolerability” of the drug and noted that adverse effects were “generally mild and transient.” The drug in question was dexfenfluramine, which was removed from the commercial market 18 months after its subsequent U.S. Food and Drug Administration approval owing to the development of valvular heart disease and primary pulmonary hypertension in a subset of patients (3,4).
This experience and many others (5) have forced us to think long and hard before making sweeping recommendations about the use of behavior-modifying drugs for the treatment of obesity.
Yet, the pediatric community confronts a serious problem: the surge of metabolic complications in obese adolescents, including impaired glucose tolerance (IGT) and type 2 diabetes, hypertension, dyslipidemia, ovarian hyperandrogenism, hepatic steatosis, and sleep apnea (6). Two recent studies highlight the concern. First (7), despite regular lifestyle counseling in a university-based clinic, one-third of obese teenagers with profound insulin resistance and IGT developed type 2 diabetes during a follow-up period of 21 months. Second (8), among Pima-Indian children and adolescents with type 2 diabetes, the rate of development of end-stage renal disease was proportional to the duration of diabetes, …
