[Rapid-acting insulin analogues]

Abstract

Two rapid-acting insulin analogues, Lys(B28), Pro(B29)-human insulin (insulin lispro) and Asp(B28)-human insulin (insulin aspart) are developed and introduced into the clinical trials or applications recently. The replacement of the natural amino acid sequence at the position 28 of the B-chain of human insulin results in an insulin molecule with reduced self association. Proline at position B28 near the COOH terminal of the B chain of human insulin is important for the dimerization of insulin molecules. These two insulin analogues exist in solution as a monomeric form and display faster pharmacodynamic action than human regular insulin. In healthy volunteers when injected subcutaneously, serum insulin concentration peaks more than twice higher and in less than half the time, compared to regular insulin. The glucose infusion rate to maintain the euglycemia level peaked in about half the time, but the total glucose infused during the euglycemic clamp is not significantly different from that of regular insulin. These rapid absorbed insulin analogues significantly inhibited the postprandial plasma glucose excursion more effectively even injected just before each meal in type 1 diabetic patients. The shorter duration of insulin action reduced the risk of severe hypoglycemia in nighttime or late postprandial time. The long-term treatment with this analogues improved HbA1c levels. Use of these insulin analogues as a preprandial bolus injection improves the quality of life of insulin-treated patients.