Pourquoi et comment l'insuline glargine U300 conduit à un état d'équilibre rapide sans effet cumulatif ?

From the present introduction to the market and the marketing in the near future of new ultra-long acting insulin analogues, there arises the question as to know whether such insulin preparations can exert cumulative effects, which in turn can be responsible for adverse events. To answer this question we have analyzed the data provided by studies on pharmacodynamics of insulin glargine U300. Taking as an example the case of an individual who receives 30 units of glargine U300 on the first day and who is submitted to repeated injections with this new formulation at a daily dose of 30 units throughout the following days, a steady state is achieved as early as the second day. On the subsequent days, the insulin utilization remains constant at 30 units per day. During the 24-h period that follows any injection of glargine U300, 80% (24 units) are provided by the administered dose. To this contribution it is necessary to add the 20% (6 units) that were not utilized on the preceding day. Therefore, in any situation, the total daily dose utilized is plateauing at the constant level.