title: Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study.
abstract: OBJECTIVE
  To study whether metformin reduces obesity, homeostasis model assessment for insulin resistance index (HOMA-IR), and the metabolic syndrome (MtS) in obese European adolescents in addition to previous unsuccessful lifestyle intervention.
  
  
  METHODS
  After 6 months of multiprofessional lifestyle intervention, 70 out of 86 adolescents without improvement in body mass index (BMI) and HOMA-IR were randomized into either the placebo (n=34) or the metformin group (2×500 mg/day, n=36) in addition to ongoing lifestyle intervention for another 6 months.
  
  
  RESULTS
  Age was 13.8 years, BMI was 33.1 kg/m(2), 65% were female, and 89% were Caucasians. During lifestyle intervention alone, BMI and HOMA-IR deteriorated significantly. In the subsequent medication period, HOMA-IR and fasting insulin improved similarly in the placebo and metformin groups (HOMA-IR decreased 73 vs 54% respectively in metformin versus placebo; P=0.048), but BMI remained unchanged. The insulin sensitivity index, however, only improved in the metformin group. High fasting insulin is correlated with a subsequent BMI increase irrespective of the medication. MtS remained unchanged.
  
  
  CONCLUSIONS
  Obese European adolescents' insulin sensitivity improved without weight change during placebo or metformin intervention in addition to lifestyle intervention. Most differences did not reach statistical significance, probably due to improved compliance with lifestyle intervention as a placebo effect. In addition, the metformin dose may be too low.
authors.affiliation: Department of Pediatric Endocrinology and Diabetology, Charité Children's Hospital, Universitätsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany. susanna.wiegand@charite.de
authors.forename: Susanna
authors.initials: S
authors.lastname: Wiegand
authors.forename: Dagmar
authors.initials: D
authors.lastname: l'Allemand
authors.forename: Hanna
authors.initials: H
authors.lastname: Hübel
authors.forename: Heiko
authors.initials: H
authors.lastname: Krude
authors.forename: Mareike
authors.initials: M
authors.lastname: Bürmann
authors.forename: Peter
authors.initials: P
authors.lastname: Martus
authors.forename: Annette
authors.initials: A
authors.lastname: Grüters
authors.forename: Reinhard W
authors.initials: RW
authors.lastname: Holl
mesh_terms: D000293:Adolescent; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D002648:Child; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D009765:Obesity / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D010919:Placebos / Q000627:therapeutic use*
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D010919:Placebos; D008687:Metformin