Reply to Besançon et al. regarding ‘Marked improvement in <scp>HbA1c</scp> following introduction of biosimilar insulin to treatment regimen of children and youth with type 1 diabetes in Mali: A randomised controlled trial’

Reply to Besanon et al. regarding 'Marked improvement in HbA1c following introduction of biosimilar insulin to treatment regimen of children and youth with type 1 diabetes in Mali: A randomised controlled trial'We read with great interest Besanon and colleagues' recent clinical trial 'Marked improvement in HbA1c following introduction of biosimilar insulin to treatment regimen of children and youth with type 1 diabetes in Mali: a randomised controlled trial'. 1 In this study, 260 participants <25 years old diagnosed with T1D were randomised 1:1 to either continue receiving their current therapy or switch to a basal-bolus analogue insulin regimen with a primary outcome of HbA1c.This outcome was assessed at baseline and then quarterly for 1 year.To be eligible for the study, the participants must have been diagnosed with T1D 12 months prior and had to be using Humulin NPH and R, or a premixed insulin (30/70 R/NPH).The trial ultimately found that the mean HbA1c decreased by ~30% in the intervention group, compared to a 6.1% reduction in the control group, with high statistical significance.Moreover, the proportion of participants with HbA1c 130 mmol/mol (14%) decreased from 38.5% to 0% in the intervention group, and from 40.6% to 21.9% in the control group, also a significant difference.Hence, the authors concluded that, 'Switching to a basal-bolus insulin regimen including biosimilar glargine resulted in marked improvements in HbA1c and diabetic ketoacidosis episodes'.This study has several methodological features that may lead to a misinterpretation of these benefits, attributing them solely to differences in insulin type (namely, analogue insulin versus human insulin) for T1D management in this population.First, more than 70% of the participants in the control group continued to receive a premix insulin during the study period.As shown previously, this obscures to what extent the findings reflect differences in glycaemic control achieved by a twice daily premix insulin regimen compared to a basal-bolus regimen, irrespective of whether human or analogue insulin products are used. 2Second, and relatedly, those in the intervention group received a higher mean total daily dose of insulin throughout the study, as noted by the authors, and administered 4.0 injections per day on average compared to 2.4 per day among