Pharmacokinetics and pharmacodynamics of basal insulins

The two basal insulin analogs, insulin glargine and insulin detemir, were developed to ameliorate the well-known limitations of NPH insulin. In contrast to rapid-acting analogs, which differ exclusively in terms of primary structure while sharing similar pharmacokinetics (PK) and pharmacodynamics (PD), the two long-acting insulin analogs are different chemical and structural entities, exhibiting distinct modes of protracting the insulin effect. So far, PK and PD studies of long-acting analogs have often shown conflicting results, pointing out different conclusions, thereby leading to animated controversies. The methods used in the evaluation of basal insulins might have been partially responsible as, although the euglycemic clamp technique has been broadly acknowledged to be the "gold standard" reference to assess the glucose-lowering effect of an insulin preparation, its execution and interpretation might have been substantially different across studies, in various methodological and analytical aspects, ultimately providing an explanation for some of these controversies. This review will present and describe the basic methods used in the evaluation of basal insulins and will critically summarize the points that might have been responsible for the different outcomes. The findings of glucose clamp studies demonstrate that the two long-acting insulin analogs are different, to some extent, in both their PK and PD profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well.