title: The effect of adding metformin to insulin therapy for type 1 diabetes mellitus children: A systematic review and meta-analysis.
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.
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Reem A
authors.identifier: http://orcid.org/0000-0002-5304-3528
authors.initials: RA
authors.lastname: Al Khalifah
authors.affiliation: Department of Pediatrics, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Abdulrahman
authors.initials: A
authors.lastname: Alnhdi
authors.affiliation: Department of Pediatrics, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Hassan
authors.initials: H
authors.lastname: Alghar
authors.affiliation: Department of Pediatrics, King Saud University, Riyadh, Saudi Arabia.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Alanazi
authors.affiliation: Department of Pediatrics, Universidad de Antioquia, Medellin, Colombia.|Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada.
authors.forename: Ivan D
authors.identifier: http://orcid.org/0000-0002-0751-8932
authors.initials: ID
authors.lastname: Florez
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016903:Drug Monitoring; D004359:Drug Therapy, Combination / Q000009:adverse effects; D019317:Evidence-Based Medicine; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D007333:Insulin Resistance; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D050177:Overweight / Q000150:complications / Q000517:prevention & control; D063766:Pediatric Obesity / Q000150:complications / Q000517:prevention & control; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; C517652:hemoglobin A1c protein, human
keywords: insulin resistance; metformin; pediatrics; systematic reviews; type 1 diabetes