Insulin analogs with improved pharmacokinetic profiles

The aim of insulin replacement therapy is to normalize blood glucose in ord er to reduce the complications of diabetes. The pharmacokinetics of the tra ditional insulin preparations, however, do not match the profiles of physio logical insulin secretion. The introduction of the rDNA technology 20 years ago opened new ways to create insulin analogs with altered properties, Fas t-acting analogs are based on the idea that an insulin with less tendency t o self-association than human insulin would be more readily absorbed into t he systemic circulation. Protracted-acting analogs have been created to mim ic the slow, steady rate of insulin secretion in the fasting state. The pre sent paper provides a historical review of the efforts to change the physic ochemical and pharmacological properties of insulin in order to improve ins ulin therapy. The available clinical studies of the new insulins an surveye d and show, together with modeling results, that new strategies for optimal basal-bolus treatment are required for utilization of the new fast-acting analogs. (C) 1999 Elsevier Science B.V. All rights reserved.