Dr. Richard DiMarchi and The Discovery of Insulin Lispro

The discovery of the human insulin analog, insulin lispro (LysB28ProB29), by Dr. Richard DiMarchi and his research team at Eli Lilly and Company is perhaps the most significant recent advances involving the treatment of diabetes mellitus. A group of metabolic diseases characterized by hyperglycemia, diabetes mellitus was put on the forefront medical science following an international conference in Monaco in 1985 by the Juvenile Diabetes Foundation International, which called for the development of fast-acting insulin analogs that mimicked the physiological effects of human insulin (1). While human insulin had been commercially prepared by Eli Lilly and Company since 1923, the efficacy of subcutaneous injections of human insulin was limited†¦show more content†¦As seen in Figure 2, lispro and human insulin were virtually identical in their interactions with both insulin and IGF-I receptors (3). The change in the primary structure of insulin Fig. 2. Affinities of regular insulin, lispro, and IGF-I for the insulin receptor and IGF-I receptor (4). altered the physical properties of insulin, but the biological properties that allowed for the proper metabolic response in the body were conserved. Because of lispro’s ability to both rapidly dissociate and efficiently bind to insulin receptors, it is able to peak more rapidly and disappear at a faster rate in the body compared to regular insulin (5). This finding was highly significant for two reasons as it pertains to insulin therapy for diabetics. First, the rapid action profile allows for the injection of lispro just prior to a meal, creating a more convenient regimen for diabetics. Second, and perhaps more importantly, the quick disappearance of lispro form the bloodstream decreases the likelihood of postprandial hypoglycemia. Regular insulin levels peak around 3 to 4 hours following injection, and continue to lower glucose levels even beyond 6 hours (4), creating a risk for hypoglycemia. The delicate balance between prevention of hyperglycemia and hypoglycemia has been a principle issue in the treatment of diabetes. A study in Italy found that when regular insulin was administered 5 minutes prior to a meal, glucose levels was in excess of 10