Effects of Metformin on Body Weight and Body Composition in Obese Insulin-Resistant Children
A Randomized Clinical Trial
- Jack A. Yanovski1,
- Jonathan Krakoff2,
- Christine G. Salaita3,
- Jennifer R. McDuffie1,
- Merel Kozlosky3,
- Nancy G. Sebring3,
- James C. Reynolds4,
- Sheila M. Brady1 and
- Karim A. Calis1,5
- 1Unit on Growth and Obesity, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, Maryland
- 2Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Bethesda, Maryland
- 3Department of Nutrition, Hatfield Clinical Research Center, National Institutes of Health, Bethesda, Maryland
- 4Department of Diagnostic Radiology and Imaging Sciences, Hatfield Clinical Research Center, National Institutes of Health, Bethesda, Maryland
- 5Department of Pharmacy, Hatfield Clinical Research Center, National Institutes of Health, Bethesda, Maryland
- Corresponding author: Jack A. Yanovski, .
OBJECTIVE Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions, including abnormalities in glucose homeostasis in adolescents, but there are few data evaluating the efficacy of metformin among younger children. Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children, who are insulin-resistant.
RESEARCH DESIGN AND METHODS This study was a randomized double-blind placebo-controlled trial consisting of 100 severely obese (mean BMI 34.6 ± 6.6 kg/m2) insulin-resistant children aged 6–12 years, randomized to 1,000 mg metformin (n = 53) or placebo (n = 47) twice daily for 6 months, followed by open-label metformin treatment for 6 months. All children and their parents participated in a monthly dietitian-administered weight-reduction program.
RESULTS Eighty-five percent completed the 6-month randomized phase. Children prescribed metformin had significantly greater decreases in BMI (difference −1.09 kg/m2, CI −1.87 to −0.31, P = 0.006), body weight (difference −3.38 kg, CI −5.2 to −1.57, P < 0.001), BMI Z score (difference between metformin and placebo groups −0.07, CI −0.12 to −0.01, P = 0.02), and fat mass (difference −1.40 kg, CI −2.74 to −0.06, P = 0.04). Fasting plasma glucose (P = 0.007) and homeostasis model assessment (HOMA) insulin resistance index (P = 0.006) also improved more in metformin-treated children than in placebo-treated children. Gastrointestinal symptoms were significantly more prevalent in metformin-treated children, which limited maximal tolerated dosage in 17%. During the 6-month open-label phase, children treated previously with placebo decreased their BMI Z score; those treated continuously with metformin did not significantly change BMI Z score further.
CONCLUSIONS Metformin had modest but favorable effects on body weight, body composition, and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program.
Clinical trial reg. no. NCT00005669, clinicaltrials.gov.
The findings and conclusions in this report are those of the authors and do not necessarily represent those of the National Institutes of Health or the Indian Health Service.
- Received August 20, 2010.
- Accepted November 1, 2010.
- © 2011 by the American Diabetes Association.
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