DISCOVERY AND DEVELOPMENT OF INSULIN LISPRO

Insulin lispro, a human insulin analog created by reversing the native amino acid sequence from pro(B28)Lys(B29) to Lys(B28)Pro(B29), is a r apid-acting insulin with a short duration of action due to its weakene d propensity to self-associate into dimers. As a mealtime insulin, it offers people with insulin-requiring diabetes a more flexible lifestyl e and ultimately better blood glucose control. This is in contrast to regular human insulin which must be administered 30-45 minutes before meals to allow sufficient time for the insulin hexamer complex to diss ociate into absorbable dimer and monomer subunits. Contrary to the pre vailing understanding of monomeric analogs, both regular human insulin and insulin lispro exist in their respective formulations as hexamers that are stabilized with zinc ions and phenolic preservatives to assu re 2 years of shelf life at 4 degrees C. The insulin lispro formulatio n differs, however, in that its hexamer complex dissociates into monom er subunits virtually instantaneously upon injection into the subcutis , resulting in a plasma absorption profile indistinguishable from that of a pure monomeric insulin. (C) 1998 Prous Science. All rights reser ved.