[Insulin analogs].

The present insulin preparations are not ideal for diabetes therapy by subcutaneous administration, subcutaneous insulin absorption is too slow to mimic the normal rapid increments of insulin in blood in response to nutrient intake. The absorption of insulin from subcutaneous tissue is influenced by many factors, among which the association state of insulin pharmaceutical form (hexameric) is the most important. This review describes the properties of insulin analogues, both rapid-acting and long-acting insulin analogues, designed by recombinant DNA technology with the aim of ameliorating absorption properties. Rapid-acting insulin analogues are characterised by one or a few amino acid substitutions to reduce intermolecular binding responsible for self-association. Because of largely reduced self-association they are absorbed substantially faster after subcutaneous injections than current regular insulin and determine lower insulin levels late after injection; thus short-acting analogues can be given with the meal and can minimise late hypoglycaemia. Long-acting insulin analogues have a slow absorption, providing constant basal insulinemic levels with lower day-to-day variation than current long-acting insulins. These properties are obtained by adding positive and/or removing negative charges thus increasing the isoelectric point of the molecule to about 7. In conclusion, insulin analogues represent an important goal in the therapy of diabetes and they can be a real opportunity for ameliorating glycaemic control.