Insulin analogues in the management of diabetes

Insulin therapy has been strongly influenced by the results of the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS), both of which support intensive antidiabetic therapy. Conventional insulin therapy can be limited, due to the difficulty in achieving tight glycemic control in people with diabetes, which is crucial to reducing the risk of long-term complications associated with diabetes. In recent years, three short-acting (insulin lispro, insulin aspart and insulin glulisine) and two long-acting (insulin glargine and insulin detemir) recombinant analogues of regular human insulin have been developed for the management of diabetes. Short-acting insulin analogues are an alternative to regular human insulin before meals. Compared with regular human insulin, these new short-acting insulin analogues show faster subcutaneous absorption, a more rapid onset of activity and a shorter duration of action. As a result of these pharmacokinetic differences, an improved postprandial glycemic control is achieved, without increasing the risk of hypoglycemia. In addition, these insulin analogues can be administered immediately before a meal, thereby synchronizing insulin administration and food absorption. The long-acting insulin analogue insulin glargine was developed to provide basal insulin levels for 24 h when administered once daily at bedtime. Compared with previous intermediate- or long-acting conventional insulin, insulin glargine shows a flat profile of plasma insulin levels with no prominent peak. The use of this long-acting insulin analogue appears to be associated with a reduced incidence of hypoglycemia, especially at night. Insulin detemir is another basal insulin that may reduce nocturnal hypoglycemia and variability in glycemic values. The availability of these new insulin analogues has the potential to significantly improve long-term control over blood glucose in diabetic patients.