title: Effects of metformin on body weight and body composition in obese insulin-resistant children: a randomized clinical trial.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  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.
authors.affiliation: Unit on Growth and Obesity, Program in Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Bethesda, Maryland, USA. jy15i@nih.gov
authors.forename: Jack A
authors.initials: JA
authors.lastname: Yanovski
authors.forename: Jonathan
authors.initials: J
authors.lastname: Krakoff
authors.forename: Christine G
authors.initials: CG
authors.lastname: Salaita
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: McDuffie
authors.forename: Merel
authors.initials: M
authors.lastname: Kozlosky
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Sebring
authors.forename: James C
authors.initials: JC
authors.lastname: Reynolds
authors.forename: Sheila M
authors.initials: SM
authors.lastname: Brady
authors.forename: Karim A
authors.initials: KA
authors.lastname: Calis
mesh_terms: D001823:Body Composition / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects*; D002648:Child; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin