title: Metformin as an adjunct therapy in adolescents with type 1 diabetes and insulin resistance: a randomized controlled trial.
abstract: OBJECTIVE
  To evaluate whether, in adolescents with type 1 diabetes, the addition of metformin to insulin and standard diabetes management results in 1) higher insulin sensitivity and 2) lower HbA1c, fasting glucose, insulin dosage (units per kilogram per day) and BMI.
  
  
  METHODS
  This was a randomized, placebo-controlled 3-month trial of metformin therapy in 27 adolescents with type 1 diabetes, high insulin dosage (>1 unit. kg(-1). day(-1)), and HbA1c >8%, with measurements of insulin sensitivity (by frequently sampled intravenous glucose tolerance test [FSIGT]), HbA1c, insulin dosage, and BMI at the onset and end of treatment.
  
  
  RESULTS
  At t = 0, HbA1c was 9.2 +/- 0.9%, insulin dosage was 1.2 +/- 0.2 units. kg(-1). day(-1), fasting glucose was 10.6 +/- 2.4 mmol/l, and BMI was 24.2 +/- 3.9 kg/m2 (means +/- SD), with no difference between the metformin and placebo groups. At the end of the study, HbA1c was 0.6% lower in the metformin group than in the placebo group (P < 0.05). This was achieved at lower daily insulin dosages (metformin group -0.14 +/- 0.1 vs. placebo group 0.02 +/- 0.2 units. kg(-1). day(-1); P < 0.05), with no significant change in BMI. Fasting glucose levels improved significantly in the metformin group (P < 0.05). Change in insulin sensitivity, measured by FSIGT, was not significantly different between the two groups at study end. Mild hypoglycemia occurred more frequently in the metformin-treated than in the placebo subjects (1.75 +/- 0.8 vs. 0.9 +/- 0.4 events. patient(-1). week(-1); P = 0.03). There were no differences in frequency of severe hypoglycemic episodes or gastrointestinal complaints between the two groups.
  
  
  CONCLUSIONS
  Metformin treatment lowered HbA1c and decreased insulin dosage with no weight gain in teens with type 1 diabetes in poor metabolic control. Changes in insulin sensitivity were not documented in this study using the FSIGT. Long-term studies will determine whether these improvements are sustained and whether certain subgroups accrue greater benefit from this therapy.
authors.affiliation: Division of Endocrinology, Hospital for Sick Children, Toronto, Ontario, Canada. jill.hamilton@sickkids.ca
authors.forename: Jill
authors.initials: J
authors.lastname: Hamilton
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Cummings
authors.forename: Vera
authors.initials: V
authors.lastname: Zdravkovic
authors.forename: Diane
authors.initials: D
authors.lastname: Finegood
authors.forename: Denis
authors.initials: D
authors.lastname: Daneman
mesh_terms: D000293:Adolescent; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin