Rapid Acting Insulin Analogues

Different kinds of insulin analogues, both short acting as well as long acting, are now available which offer several benefits over human insulins including improved physiologic profile, greater convenience, reduced risk of hypoglycemia and, in some instances, less weight gain. Combined, these elements may increase a patient’s adherence to treatment, potentially increasing the level of glycemic control and improving the prognosis in patients with diabetes mellitus. Rapid-acting insulin analogues, namely aspart, lispro and glulisine have very similar pharmacokinetic profiles that mirror endogenous insulin more closely than regular human insulin. These insulin analogues can also be given closer to mealtimes and are less likely to cause hypoglycemia. While insulin lispro differs from human insulin by substitution of proline with the lysine at position 28 and lysine with proline at position 29 of the insulin β-chain, insulin aspart is designed with the replacement of proline by aspartic acid at position 28. Meanwhile, insulin glulisine is a novel rapid acting insulin analogue designed with the substitution of lysine with asparagine at position 3 and by substitution of glutamine at position 29 by lysine in the insulin β-chain. These analogues are present either in monomeric form or in very weakly bound hexameric form. They are rapidly absorbed in <30 minutes following subcutaneous injection and have a short time to peak insulin concentration of 1 hour and a shorter duration of action of 3–4 hours when compared with regular human insulin. The simplicity and efficacy of insulin analogues should help facilitate a patient’s transition to insulin therapy. Current guidelines advocate starting insulin therapy in patients who have not achieved glycemic targets or those with glycated hemoglobin greater than 8.5% and adjusting doses as necessary. InTRoduCTIon Administration of exogenous insulin in a basal-bolus regimen attempts to mimic the natural release of insulin through multiple daily injections. Although this regimen provides acceptable plasma glucose levels, the exact duplication of normal insulin secretion patterns continues to be a challenge.1-3 Mealtime injection of regular human insulin can be problematic for 2 reasons. First, the delayed onset of absorption necessitates administration of regular human insulin 30 minutes before meals, a practice that many patients do not follow because of its inconvenience. Second, the peak effect of regular insulin may not occur until 3 hours after administration, whereas plasma glucose levels usually rise more quickly after meals. This disparity in insulin and plasma glucose levels creates a brief hyperglycemic period immediately after the meal, as well as a potential hypoglycemic period 3 to 4 hours after the meal. Genetic manipulation of insulin’s amino acid sequence has produced several analogues that have significantly reduced self-association and remain monomers in solution. developmenT of InSulIn AnAlogueS The advent of recombinant DNA technology made it possible to overcome the limitations in the timeaction profile of conventional insulins. Genetic manipulation of insulin has produced new molecules commonly referred to as insulin analogues for clinical use. 2 The newer insulin analogues have potential 5 : 5