Puberty is a critical period for the development and acceleration of vascular complications in Type 1 diabetes (T1D). We have shown that metformin in addition to insulin improves vascular smooth muscle function and HbA1c in T1D children over 12 months (1). We aimed to determine if children with T1D who received metformin in a randomized controlled trial (RCT) [Trial registration ACTRN126110001148976] have a sustained vascular function improvement 3 years after ceasing metformin compared to children who received placebo. Design was a three year follow up study after completion of 12 months RCT of metformin (1 gram twice a day) vs placebo. Subjects had the same assessments for vascular function as in RCT using brachial artery ultrasound (Flow mediated dilatation [FMD] and glyceryl trinitrate mediated dilatation [GTN]) and laboratory methods. Ninety children with T1D (mean (SD) age 13.6 (2.5) years, 41 boys, median [interquartile range (IQR)] HbA1c 8.7[8.1-9.9]%/72 [65-85] mmol/mol) included in the original trial were invited to participate in the follow up. Metformin was not prescribed after the trial was completed. Fifty six adolescents have completed follow up for 3.2 (0.7) years after completion of the RCT: 27 in the original metformin group and 29 in placebo group, mean age 17.4 (S.D. 3.1) years, 27 males, mean diabetes duration of 9.9 (4.1) years and median [IQR] HbA1c of 9.2 [8.510.5] %/76  mmol/mol. There were no significant differences at baseline between the children that completed the post RCT follow up and those that did not, but completers were younger (13.3 (0.4) years vs 14.3 (0.4) years, P=0.07). Linear mixed model analysis showed that children who received Metformin in the RCT compared to placebo had an improvement in HbA1c (effect of 0.64% (95% CI −1.1, 0.1, P=0.002) and vascular smooth muscle function (GTN) independent of HbA1c (effect of 2.37 percentage units, 95% CI −0.23, 4.97, P=0.07) over the follow up period. Sensitivity analysis using multiple imputation showed similar results. As in the RCT there were no significant effects observed on endothelial function or intima media thickness. The improvement in HbA1c during 12 months of metformin intervention persisted for 3 years after discontinuation in children and adolescents with T1D. Transient use of metformin during puberty in T1D may provide ongoing benefit.
1. Anderson et al. Effect of Metformin of Vascular Function in Children With Type 1 Diabetes: A 12-month Randomized Controlled Trial. J Clin Endocrinol Metab 2017.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology