INSULIN LISPRO - A REVIEW OF ITS PHARMACOLOGICAL PROPERTIES AND THERAPEUTIC USE IN THE MANAGEMENT OF DIABETES-MELLITUS

Insulin lispro, a recombinant insulin analogue, identical to human ins ulin except for the transposition of proline and lysine at positions 2 8 and 29 in the C-terminus of the B chain. The resultant reduced capac ity for self-association in solution translates into rapid absorption of insulin lispro than human reg ular insulin from subcutaneous sites. Maximum insulin concentrations are higher and are reached earlier wit h insulin lispro than with human regular insulin, anti insulin concent rations return to baseline values more quickly with insulin lispro; co nsequently, insulin lispro has a more rapid onset and a shorter durati on od glucose-lowering activity. These pharmacological properties prov ided the rationale for comparative clinical trials of subcutaneous ins ulin lispro (administered within 15 minutes before meals, preferably i mmediately before meals) and subcutaneous human regular insulin (admin istered 20 to 45 minutes before meals) in patients with type 1 diabete s (insulin-dependent diabetes mellitus) or type 2 diabetes (non-insuli n-dependent diabetes mellitus) requiring premeal insulin therapy plus basal insulin therapy. Available clinical trials are well designed and results suggest that 1- and 2-hour postprandial blood glucose levels with insulin lispro are similar to or lower than those with human regu lar insulin 1- and 2-hour postprandial glucose excursions are similar to or less pronounced than those with human regular insulin. Glycated haemoglobin A values were generally similar with both agents. Continuo us subcutaneous insulin infusion was associated with greater improveme nts in postprandial blood glucose levels and glycated haemoglobin A1 v alues with insulin lispro than with human regular insulin. Confirmator y data are required. The incidence of hypoglycaemia with insulin lispr o was similar to or lower than that with human regular insulin. In par ticular, insulin lispro appears to be associated with a lower incidenc e of night-time and severe hypoglycaemic episodes. Evidence also sugge sts that patients perceive their quality of life to be improved proved with insulin lispro compared with human regular insulin, and that sat isfaction with treatment is greater with the insulin analogue. Thus, i n patients with type 1 or 2 diabetes requiring premeal insulin therapy , insulin lispro appears to provide greater postprandial glycaemic con trol than human regular insulin without increasing the risk of hypogly caemia. Furthermore, the reduced injection-meal interval with this age nt offers greater convenience for the patient than regular human insul in. If longer term clinical experience supports these promising result s it is likely that insulin lispro will offer important advantages ove r human regular insulin.