|
||||||
|
|
|
|
|||||||||||
|
|||||||||||||
| ||||||||||||||||||||||||||||||||||||||
Michael Freemark, MD, concedes that he was "reticent" when asked to deliver a presentation on the use of pharmacological interventions in morbidly obese pre-diabetic youth at the American Diabetes Association's 66th Annual Scientific Sessions, held June 9–13 in Washington, D.C.
"The experience with dexfenfluramine should cause us to think long and hard" about these drugs, says Freemark, chief of pediatric endocrinology at Duke University Medical Center in Durham, N.C. Dexfenfluramine's association with heart disease and hypertension caused it to be withdrawn from the commercial market.
Studies of weight-loss drugs in adults have tended to be short (few last more than 1 year), have different study designs, and show benefits only while the subjects take the drug, Freemark says. Only six randomized controlled studies of medication for weight loss have been completed in obese adolescents, showing "highly variable" efficacy, he says: one study of orlistat (Xenical, Roche),1 two of sibutramine (Meridia, Abbott),2,3 and three of metformin.4–6
Freemark says the belief of many physicians that lifestyle intervention does not work to treat obesity is "not true." Intensive lifestyle intervention through diet and exercise can increase insulin sensitivity, reduce fasting and postprandial glucose, reduce LDL and triglyceride concentrations, increase HDL levels, and reduce the risk of developing type 2 diabetes in adults.
Lifestyle changes also can result in weight loss, he says, but only if they are maintained at an intense level over the long term with highly motivated patients. When lifestyle intervention does not work, he says it may be because weight-loss goals are unclear, are directed more at obesity's complications than obesity itself, or are incompletely defined, particularly in children.
RECOMMENDATIONS
Freemark makes the following recommendations for identifying obese adolescent candidates for drug therapy: "Pharmacotherapy should be considered for adolescents when severe obesity and/or comorbidities persist despite a `good-faith effort'" to lose weight with intensive lifestyle intervention. If the family history for type 2 diabetes is particularly strong, it might be considered earlier, he says.
"A good-faith effort means that the patient has attempted to follow a low-fat/low-calorie diet recommended by a dietary counselor and has increased his or her energy expenditure through regular exercise," Freemark has written. "Unsuccessful means that the elevations of fasting or postprandial glucose persist or worsen despite lifestyle intervention."7
|
Lifestyle intervention should precede and be maintained during drug therapy, and the approach should be tailored to the individual, reflecting family history and tolerance. Also, the physician should monitor the patient closely for adverse drug effects.
Teenagers with severe insulin resistance or impaired glucose tolerance, especially those with a family history of type 2 diabetes, may benefit from treatment with metformin or orlistat, Freemark says. Metformin is the drug of choice for girls with polycystic ovary syndrome (PCOS). Sibutramine should not be prescribed for obese adolescents with hypertension, cardiovascular disease, or mood disorders.
If the patient achieves his or her weight-loss goals, the physician can reduce the dose of the drug or drop it altogether, suggests Freemark.
"But maintain lifestyle, or you can expect [weight] rebound and a
relapse of comorbidities," he says. 
References
2. Berkowitz RI, Wadden TA, Tershakovec AM, et al.: Behavior therapy
and sibutramine for the treatment of adolescent obesity: A randomized
controlled trial. JAMA 289:1805–1812, 2003.
3. 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 90:1460–1465, 2005.
4. 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 107: e55, 2001.
5. Kay JP, Alemzadeh R, Langley G, et al.: Beneficial effects of metformin in normoglycemic morbidly obese adolescents. Metabolism 50:1457–1461, 2001.[Medline]
6. 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 91:2074–2080, 2006.
7. Freemark M: Pharmacologic approaches to the prevention of type 2
diabetes in high risk pediatric patients. J Clin Endocrinol
Metab 88:3–13, 2003.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
| ||||||||||||||||||||||||||||||||||||||
|
||||||
|
| DOC News | Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |
