Échec des antidiabétiques oraux à doses maximales tolérées : Quels traitements injectables?

Secondary failure to oral antidiabetic treatments in persons with type 2 diabetes is commonly encountered in the time course of the disease several years after the time of diagnosis. In this situation, the strategy consists to reinforce the treatment by implementing injectable preparations represented by either insulins or GLP-1 receptor agonists (GLP-1 RA). The choice between these two options should be guided by weighing their potential advantages/disadvantages and by giving due consideration to three main parameters: the HbA1c, the presence/absence of excessive body weight, and the risk for hypoglycemic events. At this stage of the disease, insulin regimens are usually delivered as basal insulin therapies using once-daily injections of long-acting insulin analogues. At present, it seems more appropriate to use the longer insulin analogues that exert their activity at least over 24 hours (glargine U100) or far beyond such as the second generation of acylated insulin degludec or the new formulation of insulin glargine containing 300 units/mL. The two latter ultra-long acting insulin preparations have the same glucose-lowering effect as that of their usual comparator, glargine U100, but with a safer profile, i.e. a lower risk for hypoglycemic events. The second option consists to implement the add-on therapy with a GLP-1 RA and more specifically with short-acting preparations (exenatide, or lixisenatide), which are preferentially aimed at reducing postmeal glucose excursions. The advantage of such incretin-based therapies lies in the fact firstly that the risk of hypoglycemia remains low and secondly that the patients experience favourable effects on body weight. For all these reasons, GLP-1 RA are increasingly prescribed as add-on therapy in persons exhibiting a secondary failure to oral antidiabetic drugs (OADs) given at maximal tolerated doses. In those patients who do not respond successfully to the addition of GLP-1 RA after a few month-period of treatment, it is always possible, at this stage of the disease, to consider basal insulin regimens as subsequent therapies for attempting to restore a satisfactory or even a near normal glycemic control. In any case, whether the basal insulin be immediately implemented after failure of OADs or initiated after a transient treatment with GLP-1 RA, the insulin doses should be carefully titrated to avoid as much as possible the onset of hypoglycemic episodes, especially in those patients who are considered “vulnerable”.