title: A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Metformin Therapy in Overweight/Obese Youth with Type 1 Diabetes.
abstract: BACKGROUND
  Insulin resistance has been proposed as one of the causes of poor glycemic control in overweight/obese youth with type 1 diabetes (T1D). However, the role of adjunctive metformin, an insulin sensitizer, on glycemic control in these patients is unclear.
  
  
  OBJECTIVE
  To compare the effect of metformin vs. placebo on hemoglobin A1c (HbA1c), total daily dose (TDD) of insulin, and other parameters in overweight/obese youth with T1D.
  
  
  OBJECTIVE
  Adjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D.
  
  
  METHODS
  A 9-mo randomized, double-blind, placebo controlled trial of metformin and placebo in 28 subjects (13m/15f) of ages 10-20years (y), with HbA1c >8% (64 mmol/mol), BMI >85%, and T1D > 12 months was conducted at a university outpatient facility. The metformin group consisted of 15 subjects (8 m/ 7f), of age 15.0 ± 2.5 y; while the control group was made up of 13 subjects (5m/ 8f), of age 14.5 ± 3.1y. All participants employed a self-directed treat-to-target insulin regimen based on a titration algorithm of (-2)-0-(+2) units to adjust their long-acting insulin dose every 3rd day from -3 mo through +9 mo to maintain fasting plasma glucose (FPG) between 90-120 mg/dL (5.0-6.7 mmol/L). Pubertal maturation was determined by Tanner stage.
  
  
  RESULTS
  Over the course of the 9 months of observation, the between-treatment differences in HbA1c of 0.4% (9.85% [8.82 to 10.88] for placebo versus 9.46% [8.47 to 10.46] for metformin) was not significant (p = 0.903). There were non-significant reduction in fasting plasma glucose (189.4 mg/dL [133.2 to 245.6] for placebo versus 170.5 mg/dL [114.3 to 226.7] for metformin), (p = 0.927); total daily dose (TDD) of short-acting insulin per kg body weight/day(p = 0.936); and the TDD of long-acting insulin per kg body weight per day (1.15 units/kg/day [0.89 to 1.41] for placebo versus 0.90 units/kg/day [0.64 to 1.16] for metformin) (p = 0.221). There was no difference in the occurrence of hypoglycemia between the groups.
  
  
  CONCLUSIONS
  This 9-month RCT of adjunctive metformin therapy in overweight and obese youth with T1D resulted in a 0.4% lower HbA1c value in the metformin group compared to the placebo group.
  
  
  BACKGROUND
  ClinicalTrial.gov NCT01334125.
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, Massachusetts, 01655, United States of America.
authors.forename: Benjamin Udoka
authors.initials: BU
authors.lastname: Nwosu
authors.affiliation: Department of Quantitative Health Sciences, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, Massachusetts, 01655, United States of America.
authors.forename: Louise
authors.initials: L
authors.lastname: Maranda
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, Massachusetts, 01655, United States of America.
authors.forename: Karen
authors.initials: K
authors.lastname: Cullen
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, Massachusetts, 01655, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Greenman
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, Massachusetts, 01655, United States of America.
authors.forename: Jody
authors.initials: J
authors.lastname: Fleshman
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, Massachusetts, 01655, United States of America.
authors.forename: Nancy
authors.initials: N
authors.lastname: McShea
authors.affiliation: Department of Quantitative Health Sciences, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, Massachusetts, 01655, United States of America.
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Barton
authors.affiliation: Division of Pediatric Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, Massachusetts, 01655, United States of America.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose; D017024:Chemotherapy, Adjuvant; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D009765:Obesity / Q000150:complications / Q000188:drug therapy*
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007328:Insulin; D008687:Metformin; C517652:hemoglobin A1c protein, human