Clinical effect of metformin in children and adolescents with type 2 diabetes mellitus: A systematic review and meta-analysis

To assess the clinical value and of metformin as mono-therapy versus other treatments for type 2 diabetes mellitus in children and adolescents. Major electronic databases, the reference lists of relevant articles and databases of ongoing trials were searched. Authors of reviews and metformin manufacturers were contacted in order to obtain more references and reports of unpublished trials. The methodological quality of these reports, included randomised controlled trials (RCTs) was assessed using the National Health System Centre for Reviews and Dissemination (NHS CRD) checklist. The search identified 1,825 studies. Three RCTs met the inclusion criteria. Two RCTs had been completed and one was still ongoing. In the metformin group there were significant reductions of mean change of HBA1c from baseline. It reduced by -0.71% (P = 0.0002) and in the other trial the result was reduced by -1.10 (95% CI: -1.19 to -1.01). In addition, more patients (48.1%) in the metformin group achieved good glycaemic control (<7%) at week 24. The mean changes in FPG from baseline were significantly (P < 0.05) different in the metformin group (-16.6%, for week 18 and week 24 20.6%. In the second trial there was a significant (P < 0.001) reduction in the adjusted mean of FPG from baseline in the metformin group, while there was an increase in the placebo group ( -42.9 mg/dl vs. +21.4mg/dl) with mean difference of -64.80 in favour of the metformin group. For BMI, significant (P < 0.001) differences were seen at week 12 and week 24 (0.07 and 0.55 kg(2)) for metformin and glimepiride respectively. There was no significant difference between the placebo and metformin in the other trials. For lipid value there was a significant decrease in LDL levels in the metformin group. No significant changes were found in the other lipid parameters after adjusting. There were more adverse events in the metformin group but they were not statistically significant. There was a limited but not convincing evidence to suggest that metformin can improve the glycaemic control in children and adolescent with type 2 diabetes compared with other interventions. This is may be the result of the limited number, poor quality and short duration of the included trials.