The effect of adding metformin to insulin therapy for type 1 diabetes mellitus children: A systematic review and meta-analysis

Pediatr Diabetes. 2017 Nov;18(7):664-673. doi: 10.1111/pedi.12493. Epub 2017 Feb 1.

Abstract

We aimed to assess the effectiveness of adding metformin to insulin in type 1 diabetes mellitus (T1DM) children for improving metabolic outcomes. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) conducted on children age 6 to 19 years who are diagnosed with T1DM, and examined the effect of adding Metformin to standard insulin therapy. We performed literature searches on Ovid Midline, Ovid Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) from the date of inception of the database to February 15, 2016. Two reviewers screened titles and abstracts independently, assessed full text eligibility, and extracted information from eligible trials. The primary outcome is glycated hemoglobin (HbA1c), and the secondary outcomes are health-related quality of life, body mass index (BMI), lipid profile, total insulin daily dose, hypoglycaemia, and diabetes ketoacidosis. We screened 736 studies, and included 6 RCTs with 325 patients. All RCTs were of low risk of bias, and included adolescents (mean age 15 years). The meta-analysis showed that the addition of Metformin resulted in decreased total insulin daily dose (TIDD) (unit/kg/d) (mean difference [MD] = -0.15, 95%CI, -0.24, -0.06), and reduced BMI kg/m2 (MD -1.46, 95%CI -2.54, 0.38), and BMI z-score (MD= - 0.11, 95%CI -0.21, -0.01), and similar HbA1c (%) (MD= - 0.05, 95%CI, -0.19, 0.29). The overall evidence quality was high to moderate. Current evidence does not support use of Metformin in T1DM adolescents to improve HbA1c. However, Metformin may provide modest reduction in TIDD and BMI.

Keywords: insulin resistance; metformin; pediatrics; systematic reviews; type 1 diabetes.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Drug Monitoring
  • Drug Therapy, Combination / adverse effects
  • Evidence-Based Medicine*
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hyperglycemia / prevention & control
  • Hypoglycemia / chemically induced
  • Hypoglycemia / prevention & control
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / adverse effects
  • Insulin / therapeutic use*
  • Insulin Resistance*
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Overweight / complications
  • Overweight / prevention & control
  • Pediatric Obesity / complications
  • Pediatric Obesity / prevention & control
  • Quality of Life*
  • Randomized Controlled Trials as Topic
  • Young Adult

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin
  • hemoglobin A1c protein, human
  • Metformin