Insulin analogues: new dimension of management of diabetes mellitus

Abstract

Insulin is one of the fundamental tools for the management of diabetes mellitus. All type 1 diabetic patients and most of the type 2 require the appropriate support of insulin for good glycemic control, long term healthy outcome and also to overcome the acute crisis. It is almost impossible to mimic the endogenous physiological insulin secretion curve by external administration of short acting human insulin and conventional intermediate acting insulin, neutral protamin Hagedorn (NPH), the so called basal insulin. Short acting human insulin has got a delayed onset of action, late peak and a long tail leading to postprandial hyperglycemia and late hypoglycemia. The so called basal insulin (NPH) is not truly a basal or peakless insulin. Its onset of action takes about 2 - 4 hours with a peak action and a tail. It can not maintain a constant basal level leading to premeal and fasting hyperglycemia and chance of hypoglycemia during peak action, particularly after night injection. To overcome the limitations of human insulin, during the last decade, three ultrashort acting and two long acting basal analogues have been developed by modifications of primary molecule of human insulin. The ultrashort acting analogue insulins are insulin lispro, insulin aspart and insulin glulisine. The basal analogues are insulin glargin and insulin detemir. The pharmacokinetic profiles of novel analogue molecules provide a better opportunity to mimic a physiological pattern of insulin administration, better glycemic control, less chance of hypoglycemia, greater flexibility and a healthy longterm outcome.