Effects of Metformin on Body Weight and Body Composition in Obese Insulin-Resistant Children: A Randomized Clinical Trial

• Published in: Diabetes (New York, N.Y.) Vol. 60; no. 2; pp. 477 - 485
• Main Authors: YANOVSKI, Jack A, KRAKOFF, Jonathan, SALAITA, Christine G, MCDUFFIE, Jennifer R, KOZLOSKY, Merel, SEBRING, Nancy G, REYNOLDS, James C, BRADY, Sheila M, CALIS, Karim A
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-02-2011
• Subjects: Adults; Age; Biological and medical sciences; Body composition; Body Composition - drug effects; Body Weight - drug effects; Child; Childhood obesity; Complications and side effects; Diabetes; Diabetes. Impaired glucose tolerance; Dosage and administration; Double-Blind Method; Drug therapy; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; FDA approval; Female; Glucose; Homeostasis; Humans; Hypoglycemic Agents - pharmacology; Hypoglycemic Agents - therapeutic use; Insulin Resistance; Male; Medical sciences; Metabolic diseases; Metabolic syndrome; Metformin; Metformin - pharmacology; Metformin - therapeutic use; Obesity; Obesity - drug therapy; Obesity in children; Obesity Studies; Pediatrics; Physiological aspects; Prevention; Research design; Risk factors; Treatment Outcome; Weight control; United States; Endocrinopathy; Human; Obesity; Pancreatic hormone; Diabetes mellitus; Body weight; Nutrition disorder; Insulin; Body composition; Biguanides; Clinical trial; Metformin; Child; Nutritional status
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db10-1185

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.
This study was a randomized double-blind placebo-controlled trial consisting of 100 severely obese (mean BMI 34.6 ± 6.6 kg/m(2)) 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.
Eighty-five percent completed the 6-month randomized phase. Children prescribed metformin had significantly greater decreases in BMI (difference -1.09 kg/m(2), 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.
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.