SAN FRANCISCO — The epidemic of childhood obesity shows no signs of abating, and studies have demonstrated only modest results from diet and exercise, unless an intensive boot-camp approach is used, Robert H. Lustig, M.D., said at a meeting on clinical pediatrics, sponsored by the University of California, San Francisco.
Intensive treatment—that is, pharmacotherapy or surgery—is indicated in an adolescent whose BMI is greater than two standard deviations from the norm for his or her age, and who has at least one significant comorbidity, said Dr. Lustig of UCSF.
Such comorbidities include metabolic, orthopedic, and cardiopulmonary complications as well as psychological distress, he said, and the majority of obese adolescents have at least one of these.
Unfortunately, pharmacotherapy for obesity has a dubious history. Drugs used in the past, such as thyroid hormone, dinitrophenol, amphetamine, fenfluramine, phenylpropanolamine, and ephedra are well known for significant complications, including death. In addition, many clinicians are hesitant to prescribe drugs to children or adolescents when their long-term effects remain unknown.
Given that obesity can result from a number of underlying conditions and the variable results of many pharmacotherapies, the trick is to pick a drug that matches the patient's characteristics, said Dr. Lustig. He discussed four available drugs, two of which are approved by the Food and Drug Administration for use in children:
▸ Sibutramine (Meridia) is an anorectic agent. Sibutramine should complement a program of diet and exercise. Studies of adolescents who were given sibutramine have shown that they had significant weight loss, especially in the first 6 months. The FDA has approved the drug for use in patients over age 16 years.
Responses to sibutramine are highly variable, however, and few predictors of response have been identified. Moreover, side effects can be significant. In one study, 19 of 43 adolescents had mild hypertension and tachycardia in response to sibutramine, and 5 required discontinuation of the drug.
Other side effects include insomnia, anxiety, headache, depression, and the risk of serotonin syndrome when used in combination with certain other drugs. Sibutramine should not be routinely used in adolescents, said Dr. Lustig.
▸ Orlistat (Xenical) is a pancreatic lipase inhibitor. This drug decreases intestinal fat absorption, and is approved for use in children above age 12 years. Orlistat, in combination with behavioral intervention, results in significant weight loss over 4 months, according to a study of 534 subjects. However, children taking orlistat regained lost weight within a year, although they still remained significantly lighter than the children taking placebo, who gained weight.
Unless fat restrictions can be maintained, side effects include flatulence, diarrhea, and anal leakage.
▸ Metformin (Glucophage) is another drug approved for use in children. It reduces hepatic gluconeogenesis, increases hepatic insulin sensitivity, and lowers fasting insulin levels.
This drug is approved for use in type 2 diabetes mellitus, but not specifically for obesity. Nevertheless, studies have shown that metformin decreases food intake, reduces fat stores, improves lipid profiles, inhibits progression from impaired glucose tolerance to type 2 diabetes, and reduces cardiovascular morbidity and mortality in adults with diabetes.
In obese adolescents with impaired insulin sensitivity, studies have demonstrated significant decreases in BMI even when metformin is administered without dietary restrictions. The drug may be especially useful in adolescents taking psychotropic medications such as olanzapine, risperidone, quetiapine, or valproate.
The drug is most useful in adolescents who have severe insulin resistance, but not those who are insulin sensitive, Dr. Lustig said. Another group that may benefit may be obese girls with polycystic ovarian syndrome.
Metformin's side effects include abdominal discomfort that lasts for about 1 month, rare lactic acidosis, and urinary losses of B vitamins. Dr. Lustig said that all patients taking metformin should also take a daily multivitamin.
▸ Octreotide (Sandostatin) inhibits the opening of calcium channels in beta cells and reduces glucose-dependent insulin secretion.
Not approved for use in obese adolescents, octreotide seems especially effective in children with “hypothalamic obesity” arising from insults to the central nervous system.
Side effects include transient GI distress and gallstones, which can be prevented by ursodiol. Other limitations include its high cost and the requirement for parenteral administration.