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PLoS One. 2015 Sep 14;10(9):e0137525. doi: 10.1371/journal.pone.0137525. eCollection 2015.

A Randomized, Double-Blind, Placebo-Controlled Trial of Adjunctive Metformin Therapy in Overweight/Obese Youth with Type 1 Diabetes.

Author information

1
Division of Pediatric Endocrinology, Department of Pediatrics, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, Massachusetts, 01655, United States of America.
2
Department of Quantitative Health Sciences, University of Massachusetts Medical School, 55 Lake Avenue N, Worcester, Massachusetts, 01655, United States of America.

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.

PMID:
26367281
PMCID:
PMC4569440
DOI:
10.1371/journal.pone.0137525
[Indexed for MEDLINE]
Free PMC Article

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