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/m (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.

Effect of metformin on glycaemic control in patients with type 1 diabetes: A meta‐analysis of randomized controlled trials

“…Our study on adjunctive metformin use in the general population with T1D reached similar conclusions to a systematic review among adolescents and a meta‐analysis of 6 RCTs . A recent meta‐analysis of 325 participants concluded that metformin reduced the TIDD and BMI but not HbA1c values in adolescents with T1D .…”

Metformin added to intensive insulin therapy improves metabolic control in patients with type 1 diabetes and excess body fat

“…Reduced insulin requirement following use of high metformin doses (2550 mg/d) in patients with type 1 diabetes was also documented in a study by Pagano et al 30 Furthermore, a meta--analysis by Khalifah et al 31 showed that add -on metformin treatment reduced total daily insulin dose and BMI in children.…”

What role for metformin in type 1 diabetes?

“…16 The addition of metformin to insulin did not reduce HbA 1c levels but resulted in decreased total insulin daily dose (MD −0.16 units/kg, 95% CI −0.22 to −0.11; six studies, 325 participants) and reduced body mass index (MD −1.5kg/m 2 , 95% CI −2.5 to −0.4; four studies, 159 participants).…”