Abstract
Childhood obesity is emerging as a major public health threat, with adverse implications on the health of individuals and long-term costs to society. Family-based lifestyle interventions with behavioral modification, diet and exercise form the mainstay of treatment. Pharmacologic treatment may be considered in selected subjects, especially in the presence of significant and severe comorbidities, when lifestyle intervention has failed to achieve weight reduction. Orlistat and sibutramine are FDA-approved for treatment of pediatric obesity; metformin may be considered in the presence of clinically significant insulin resistance. Evidence is lacking on the appropriate duration of medical therapy and optimal combination with lifestyle intervention. Lack of coverage of medications by insurance and high out-of-pocket costs may be limiting factors to some families. Adverse effects necessitate careful monitoring and may lead to discontinuation of medication. Pharmacologic agents with novel mechanisms of action offer hope of improved efficacy, tolerability and safety.
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References
Ogden CL, Carroll MD, Curtin LR, et al. Prevalence of overweight and obesity in the United States, 1999–2004. JAMA. 2006;295:1549–55.
Speiser PW, Rudolf MCJ, Anhalt H, et al. Consensus statement: childhood obesity. J Clin Endocrinol Metab. 2005;90:1871–87.
Baker JL, Olsen LW, Sorensen TIA. Childhood body mass index and the risk of coronary heart disease in adulhood. N Engl J Med. 2007;357:2329–37.
Bibbins-Domingo K, Coxson P, Pletcher MJ, et al. Adolescent overweight and future adult coronary heart disease. N Engl J Med. 2007;357:2371–9.
Barlow SE, the Expert Committee. Expert Committee recommendations regarding the prevention, assessment and treatment of child and adolescent overweight and obesity: summary report. Pediatrics. 2007;120(4):S164–92.
Ogden CL, Carroll MD, Flegal KM. High body mass index for age among US children and adolescents, 2003–2006. JAMA. 2008;299:2401–5.
Spear BA, Barlow SE, Ervin C, et al. Recommendations for treatment of child and adolescent overweight and obesity. Pediatrics. 2007;120:S254–88.
August GP, Caprio S, Fennoy I, et al. Prevention and treatment of pediatric obesity: an endocrine society clinical practice guideline based on expert opinion. J Clin Endocrinol Metab. 2008;93:4576–99.
Sjostrom L, Rissanen A, Andersen T, et al. Randomized placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet. 1998;352:167–72.
Hauptman J, Lucas C, Boldrin MN, et al. Orlistat in the long-term treatment of obesity in primary care settings. Arch Fam Med. 2000;9:160–7.
McDuffie JR, Calis KA, Uwaifo GI, et al. Three-month tolerability of orlistat in adolescents with obesity-related comorbid conditions. Obes Res. 2002;10:642–50.
Norgren S, Danielsson P, Jurold R, et al. Orlistat treatment in obese prepubertal children: a pilot study. Acta Paediatr. 2003;92:666–70.
McDuffie JR, Calis KA, Uwaifo GI, et al. Efficacy of orlistat as an adjunct to behavioral treatment in overweight African American and Caucasian adolescents with obesity-related co-morbid conditions. J Pediatr Endocrinol Metab. 2004;17:307–19.
Ozkan B, Bereket A, Turan S, et al. Addition of orlistat to conventional treatment in adolescents with severe obesity. Eur J Pediatr. 2004;163:738–41.
Maahs D, de Serna DG, Kolotkin RL, et al. Randomized, double-blind, placebo-controlled trial of orlistat for weight loss in adolescents. Endocr Pract. 2006;12:18–28.
Chanoine J-P, Hampl S, Jensen C, et al. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA. 2005;293:2873–83.
Godoy-Matos A, Carraro L, Vieira A, et al. Treatment of obese adolescents with sibutramine: a randomized, double-blind, controlled study. J Clin Endocrinol Metab. 2005;90:1460–5.
Garcia-Morales LM, Berber A, Macias-Lara CC, et al. Use of sibutramine in obese Mexican adolescents: a 6-month, randomized, double-blind, placebo-controled, parallel-group trial. Clin Ther. 2006;28:770–82.
Berkowitz RI, Wadden TA, Tershakovec AM, et al. Behavior therapy and sibutramine for the treatment of adolescent obesity: a randomized controlled trial. JAMA. 2003;289:1805–12.
Berkowitz RI, Fujioka K, Daniels SR, et al. Effects of sibutramine treatment in obese adolescents: a randomized trial. Ann Intern Med. 2006;145:81–90.
Freemark M, Bursey D. The effects of metformin on body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. Pediatrics. 2001;107:E55.
Kay JP, Alemzadeh R, Langley G, et al. Beneficial effects of metformin in normoglycemic morbidly obese adolescents. Metabolism. 2001;50:1457–61.
Srinivasan S, Ambler GR, Baur LA, et al. Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. J Clin Endocrinol Metab. 2006;91:2074–80.
Burgert TS, Duran EJ, Goldberg-Gell R, et al. Short-term metabolic and cardiovascular effects of metformin in markedly obese adolescents with normal glucose tolerance. Pediatr Diabetes. 2008;9:567–76.
Love-Osborne K, Sheeder J, Zeitler P. Addition of metformin to a lifestyle modification program in adolescents with insulin. J Pediatr. 2008;152:817–22.
Gibson WT, Farooqi IS, Moreau M, et al. Congenital leptin deficiency due to homozygosity for the delta-133G mutation: report of another case and evaluation of response to four years of leptin therapy. J Clin Endocrinol Metab. 2004;89:4821–6.
Carrel A, Moerchen V, Myers SE, et al. Growth hormone improves mobility and body composition in infants and toddlers with Prader-Willi syndrome. J Pediatr. 2004;145:744–9.
Lustig RH, Hinds PS, Ringwald-Smith K, et al. Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebo-controlled trial. J Clin Endocrinol Metab. 2003;88:2586–92.
Despres J-P, Golay A, Sjostrom L, et al. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005;353:2121–34.
Pi-Sunyer FX, Aronne LJ, Heshmati HM, et al. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America: a randomized controlled trial. JAMA. 2006;295:761–75.
Moreira FA, Grieb M, Lutz B. Central side effects of therapies based on CB1 cannabinoid receptor agonist and antagonists: focus on anxiety and depression. Best Pract Res Clin Endocrinol Metab. 2009;23:133–44.
Levisohn PM. Safety and tolerability of topiramate in children. J Child Neurol. 2000;15(Suppl 1):S22–6.
Claudino AM, de Oliveira IR, Appolinario JC, et al. Double-blind, randomized, placebo-controlled trial of topiramate plus cognitive-behavior therapy in binge-eating disorder. J Clin Psychiatry. 2007;68:1324–32.
Gadde KM, Franciscy DM, Wagner HR, et al. Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA. 2003;289:1820–5.
Kendall DM, Riddle MC, Rosenstock J, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005;28:1083–91.
DeFronzo RA, Ratner RE, Han J, et al. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005;28:1092–100.
Anderson JW, Greenway FL, Fujioka K, et al. Bupropion SR enhances weight loss: a 48-week double-blind, placebo- controlled trial. Obes Res. 2002;10:633–41.
Jain AK, Kaplan RA, Gadde KM, et al. Bupropion SR versus placebo for weight loss in obese patients with depressive symptoms. Obes Res. 2002;10:1049–56.
McGovern L, Johnson JN, Paulo R, et al. Treatment of pediatric obesity: a systematic review and meta-analysis of randomized trials. J Clin Endocrinol Metab. 2008;93:4600–5.
Oude Luttikhuis H, Baur L, Jansen H, et al. Interventions for treating obesity in children. Cochrane Database Syst Rev. 2009;1:CD001872.
Uli N, Sundararajan S, Cuttler C. Treatment of childhood obesity. Curr Opin Endocrinol Diabetes Obes. 2008;15:37–47.
Freemark M. Pharmacotherapy of childhood obesity: an evidence-based, conceptual approach. Diabetes Care. 2007;30:395–402.
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This work was supported in part by the Healthy Kids Healthy Weight program, Rainbow Babies & Children’s Hospital (NU).
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Wald, A.B., Uli, N.K. Pharmacotherapy in pediatric obesity: Current agents and future directions. Rev Endocr Metab Disord 10, 205–214 (2009). https://doi.org/10.1007/s11154-009-9111-y
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DOI: https://doi.org/10.1007/s11154-009-9111-y