and 3 other(s)
Background and Aim: Advanced-stage type 2 diabetes (T2D) subjects may require insulin therapy in addition to oral and other injectable antidiabetic drugs. In particular, long-acting insulin analogs are used to cover basal insulin needs. However, finding the optimal individual insulin dose may be cumbersome and time demanding. In this regard, in silico testing is supportive. Here we develop a T2D simulator incorporating long-acting insulin Degludec (iDeg), as case study, aiming to provide a usable tool for guiding insulin therapy initiation in T2D subjects. Methods: We first tuned our T2D simulator (T2DS, Visentin et al., ATTD 2014) to reproduce the behavior of insulin-naive T2D subjects of a clinical study (Holst et al., J Diabetes Sci Technol 2016). Then, we developed a pharmacokinetic model describing iDeg subcutaneous absorption based on average T2D clinical data, and incorporated it into the T2DS. Finally, we performed a 52-week simulation with subjects up-titrated to optimal iDeg dose, and compared final fasting plasma glucose (f-FPG) and final iDeg dose (f-iDeg) with those of a clinical study (Zinman et al., Diabetes Care 2012). Results: After 52 weeks, in silico results were almost superimposable to clinical ones: f-FPG was 108±21 mg/dL in silico vs. 106±55 mg/dL in vivo; f-iDeg was 0.59±0.29 U/kg in silico vs. 0.59±0.35 U/kg in vivo. Conclusions: iDeg-T2DS reproduced the main findings of a clinical trial, proving its ability to describe basal insulin therapy initiation in insulin-naive T2D subjects. Hence, T2DS represents an effective way to test in silico insulin titration to optimize safety and efficacy for T2D therapy.
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