ABSTRACT
For people with type 1 or type 2 diabetes, soluble human insulin [HI] is commonly used to replace mealtime insulin by subcutaneous injection, and the protaminated form [NPH] addresses basal requirements. However, due to its intrinsic self-association, soluble HI absorption is slow, resulting in insulin kinetics that do not resemble those of normal physiology. Insulin analogues have been developed from HI to retain its metabolic action but with improved absorption kinetics. This editorial discusses the range of currently available insulin analogues and their benefits to treatment of insulin-requiring diabetes. Short-acting analogues IAsp and lispro both have alterations in their amino acid sequences which reduces self-association behavior, allowing more rapid absorption from the subcutis. These analogues can therefore be injected immediately before eating, and not 30 mm before as recommended for soluble HI. Studies have shown that IAsp and lispro provide 1better PPG control and can lower HbA[1]c further than HI. These short-acting analogues have been incorporated into 'biphasic' preparations: BIAsp 30 and Mix25, comprising rapid-acting [30% and 25%, respectively] and protaminated, intermediate-acting [70% and 75%, respectively] analogue. The biphasic profile of these premixes can thus address both mealtime and basal needs. Type 2 patients can use premix analogues from once- to thrice-daily as required, and type I patients can use them thrice-daily instead of basal-bolus therapy. Studies with type 2 patients have shown better PPG control with premixes, and more patients reach HbA[1]c targets than with human or analogue basal insulins. Furthermore, the increased risk of hypoglycaemia normally associated with intensive therapy seems to be reduced with premix treatment. The main limitations of the commonly-prescribed NPH are its characteristic plasma peak and variable absorption kinetics, which can cause hypo- or hyper glycaemia. The basal analogues IDet and lGlarg have been engineered to achieve a long duration of action with a less pronounced insulin peak. Trials have shown the efficacy of lDet and IGlarg to be similar to NPH, but with less hypoglycaemia. Moreover, IDet is associated with less pharmacokinetic/pharmacodynamic variability and less weight gain than NPH. Currently available insulin analogues can closely mimic the insulin profile of a healthy individual, thus enabling type 1 or type 2 patients to achieve and maintain glycaemic targets, with less hypoglycaemia than with conventional insulins. The mitogenic potential of insulin analogues is discussed