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A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents.
Am J Psychiatry. 2006 Dec; 163(12):2072-9.AJ

Abstract

OBJECTIVE

Second-generation, or atypical, antipsychotics effectively treat psychiatric illness in children and adolescents. However, weight gain and abnormalities in insulin sensitivity, including diabetes, complicate this therapy.

METHOD

A 16-week double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of metformin in managing weight gain in 39 subjects, ages 10-17, whose weight had increased by more than 10% during less than 1 year of olanzapine, risperidone, or quetiapine therapy. Body weight, body mass index (kilograms per square meter of height), and waist circumference were measured regularly, as were fasting insulin and glucose levels.

RESULTS

Weight was stabilized in subjects receiving metformin, while those receiving placebo continued to gain weight (0.31 kg/week). Because the study was conducted with growing children, metformin treatment resulted in reduction in z scores for both weight and body mass index. The homeostasis model assessment, a surrogate indicator of insulin sensitivity, decreased in treated subjects. Overt diabetes was diagnosed in two subjects before treatment (elevated baseline fasting glucose and insulin values) and in two placebo-treated subjects (one at week 12 and the other after study completion). One subject taking placebo developed impaired fasting glucose. Placebo treatment was associated with the need to perform oral glucose tolerance testing upon study completion, by which three additional subjects were identified with impaired glucose tolerance. No serious adverse events resulted from metformin treatment.

CONCLUSIONS

Metformin therapy is safe and effective in abrogating weight gain, decreased insulin sensitivity, and abnormal glucose metabolism resulting from treatment of children and adolescents with atypicals.

Authors+Show Affiliations

Division of Endocrinology, Cincinnati Children's Hospital Medical Center, ML 7012, 3333 Burnet Ave., Cincinnati, OH 45229, USA. david.klein@cchmc.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17151157

Citation

Klein, David J., et al. "A Randomized, Double-blind, Placebo-controlled Trial of Metformin Treatment of Weight Gain Associated With Initiation of Atypical Antipsychotic Therapy in Children and Adolescents." The American Journal of Psychiatry, vol. 163, no. 12, 2006, pp. 2072-9.
Klein DJ, Cottingham EM, Sorter M, et al. A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. Am J Psychiatry. 2006;163(12):2072-9.
Klein, D. J., Cottingham, E. M., Sorter, M., Barton, B. A., & Morrison, J. A. (2006). A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. The American Journal of Psychiatry, 163(12), 2072-9.
Klein DJ, et al. A Randomized, Double-blind, Placebo-controlled Trial of Metformin Treatment of Weight Gain Associated With Initiation of Atypical Antipsychotic Therapy in Children and Adolescents. Am J Psychiatry. 2006;163(12):2072-9. PubMed PMID: 17151157.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A randomized, double-blind, placebo-controlled trial of metformin treatment of weight gain associated with initiation of atypical antipsychotic therapy in children and adolescents. AU - Klein,David J, AU - Cottingham,Elizabeth M, AU - Sorter,Michael, AU - Barton,Bruce A, AU - Morrison,John A, PY - 2006/12/8/pubmed PY - 2007/2/17/medline PY - 2006/12/8/entrez SP - 2072 EP - 9 JF - The American journal of psychiatry JO - Am J Psychiatry VL - 163 IS - 12 N2 - OBJECTIVE: Second-generation, or atypical, antipsychotics effectively treat psychiatric illness in children and adolescents. However, weight gain and abnormalities in insulin sensitivity, including diabetes, complicate this therapy. METHOD: A 16-week double-blind, placebo-controlled trial was conducted to evaluate the effectiveness of metformin in managing weight gain in 39 subjects, ages 10-17, whose weight had increased by more than 10% during less than 1 year of olanzapine, risperidone, or quetiapine therapy. Body weight, body mass index (kilograms per square meter of height), and waist circumference were measured regularly, as were fasting insulin and glucose levels. RESULTS: Weight was stabilized in subjects receiving metformin, while those receiving placebo continued to gain weight (0.31 kg/week). Because the study was conducted with growing children, metformin treatment resulted in reduction in z scores for both weight and body mass index. The homeostasis model assessment, a surrogate indicator of insulin sensitivity, decreased in treated subjects. Overt diabetes was diagnosed in two subjects before treatment (elevated baseline fasting glucose and insulin values) and in two placebo-treated subjects (one at week 12 and the other after study completion). One subject taking placebo developed impaired fasting glucose. Placebo treatment was associated with the need to perform oral glucose tolerance testing upon study completion, by which three additional subjects were identified with impaired glucose tolerance. No serious adverse events resulted from metformin treatment. CONCLUSIONS: Metformin therapy is safe and effective in abrogating weight gain, decreased insulin sensitivity, and abnormal glucose metabolism resulting from treatment of children and adolescents with atypicals. SN - 0002-953X UR - https://www.unboundmedicine.com/medline/citation/17151157/A_randomized_double_blind_placebo_controlled_trial_of_metformin_treatment_of_weight_gain_associated_with_initiation_of_atypical_antipsychotic_therapy_in_children_and_adolescents_ DB - PRIME DP - Unbound Medicine ER -