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A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Metformin Therapy in Overweight/Obese Youth with Type 1 Diabetes
Endocrinology/Diabetes
  • Benjamin U. Nwosu, University of Massachusetts Medical School
  • Louise Maranda, University of Massachusetts Medical School
  • Karen Cullen, University of Massachusetts Medical School
  • Lisa Greenman, University of Massachusetts Medical School
  • Jody Fleshman, University of Massachusetts Medical School
  • Nancy McShea, University of Massachusetts Medical School
  • Bruce A. Barton, University of Massachusetts Medical School
  • Mary M. Lee, University of Massachusetts Medical School
UMMS Affiliation
Division of Pediatric Endocrinology, Department of Pediatrics; Department of Quantitative Health Sciences
Date
9-14-2015
Document Type
Article
Abstract
CONTEXT: 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. HYPOTHESIS: Adjunctive metformin therapy will improve glycemic control in overweight/obese youth with T1D. DESIGN, SETTING, AND PARTICIPANTS: 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. TRIAL REGISTRATION: ClinicalTrial.gov NCT01334125.
Comments

Citation: Nwosu BU, Maranda L, Cullen K, Greenman L, Fleshman J, McShea N, Barton BA, Lee MM. A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Metformin Therapy in Overweight/Obese Youth with Type 1 Diabetes. PLoS One. 2015 Sep 14;10(9):e0137525. doi: 10.1371/journal.pone.0137525. eCollection 2015. PubMed PMID: 26367281. Link to article on publisher's website

Copyright: © 2015 Nwosu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Data Availability: Our study data files are publicly deposited in the University of Massachusetts Medical School’s institutional repository, eScholarship@UMMS. The permanent links to the data are: http://dx.doi.org/10.13028/M2RP4C or http://escholarship.umassmed.edu/pediatrics_data/2/.

Keywords
  • UMCCTS funding,
  • type 1 diabetes mellitus,
  • biguanides,
  • metformin,
  • insulin resistance
PubMed ID
26367281
Creative Commons License
Creative Commons Attribution 4.0
Citation Information
Benjamin U. Nwosu, Louise Maranda, Karen Cullen, Lisa Greenman, et al.. "A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Metformin Therapy in Overweight/Obese Youth with Type 1 Diabetes" Vol. 10 Iss. 9 (2015) ISSN: 1932-6203
Available at: http://works.bepress.com/benjamin_nwosu/38/