As you pointed out, this study has the limitations of a retrospective design, a small number of patients, and a short follow-up duration. Therefore, we acknowledge that the conclusions of this study are not fully definitive; instead, we interpret the results as suggesting the need to conduct further research to identify an indicator of the subset of patients who obtain more benefits by changing from basal insulin to IDegAsp. This would be a significant advance because IDegAsp has failed to demonstrate superiority to basal insulin in the broader population of insulin-dependent patients with diabetes. Based on this pilot study, we are planning to perform a randomized controlled trial comparing IDegAsp to basal insulin in patients with a high gap between the predicted fasting plasma glucose (FPG) level and the measured FPG. With concurrent analysis using continuous glucose monitors, we expect to elucidate the relationship between the effects of IDegAsp and glycemic variability in this upcoming study. As you pointed out, precise measurements of the gap between predicted and measured FPG should be performed in a large cohort.

As you mentioned, GLP-1 agonists are beneficial for postprandial blood glucose control and have a cardiovascular protective effect [2], so the use of a combination of basal insulin and a GLP-1 agonist can effectively control postprandial blood glucose and obtain cardiovascular protective effects without increasing the number of injections [3]. However, there are still patients in whom it is difficult to use a GLP-1 agonist due to a low glomerular filtration rate or adverse effects such as gastrointestinal troubles [2]. Most of all, the eventual failure of GLP-1 therapy leads to multiple daily insulin injections, which would involve a mixed regimen such as IDegAsp [4].

Thank you again for your comments on our paper. If you have any other comments or questions, please feel free to contact me.