Reducing hypoglycaemia with insulin analogues.
Numerous studies have demonstrated that tight glycaemic control reduces long-term complications in both Type 1 and Type 2 diabetes. However, current intensive insulin regimens increase the risk of hypoglycaemia, dissuading many attempting this approach. Normal physiological insulin profiles consist of a stable, basal component and meal-related surges in secretion. Conventional insulin regimens cannot mimic this profile accurately due to pharmacokinetic limitations. Human insulin has a slow onset of action, thus patients are advised to inject about 30 min before a meal, ensuring peak insulin concentrations coincide with postprandial glucose excursions. This is clearly impractical for many and can lead to pre-meal hypoglycaemia if the meal is delayed. Furthermore, it only partially overcomes the unphysiological insulin profile and patients experience postprandial hyperglycaemia and are vulnerable to postabsorptive hypoglycaemia. Insulin aspart and insulin lispro are rapid-acting analogues that allow a more physiological replacement of mealtime insulin secretion. They reduce postprandial glucose and usefully reduce the incidence of hypoglycaemia when used in a basal-bolus regimen in tightly controlled patients. Pre-mixed insulins, containing a combination of rapid-acting and intermediate-acting insulin, are widely used, particularly in Type 2 diabetes. They have limitations achieving tight glucose targets but early data suggest that the combination of 30% insulin aspart and 70% protaminated insulin aspart may also reduce severe hypoglycaemia. On-going clinical trials will establish whether they can be used to achieve better glycaemic control with less hypoglycaemia.