Endocrine Abstracts

The advent of insulin almost 80 years ago revolutionised the treatment of diabetes and must be one of the great achievements of twentieth century medicine. Since then, there has been an increasing understanding of the need to attain and uphold near normoglycaemia to delay the onset and retard the progression of diabetic complications. Major advances in the understanding of the molecular assembly, biological activity and therapeutic properties of insulin have led to the many development to the formulations and delivery of insulin. A key innovation has been the development of insulin analogues. These are insulin molecules whose structure has been altered in order to improve its pharmacokinetic and pharmacodynamic properties compared with regular human insulin, whilst preserving its biological effects and safety profile. The first successfully marketed insulin analogue was the rapid acting analogue insulin lispro. This was followed by the rapid acting insulin analogue insulin aspart. Another rapid acting insulin analogue, insulin glulisine, is currently in development. These analogues are more rapidly absorbed from the subcutaneous tissue and are active for a shorter period in comparison to regular human insulin. These analogues also consistently restrict postprandial glucose fluctuations in comparison to human insulin when injected immediately before food. Another benefit of the rapid acting insulin analogues is a reduction in severe hypoglycaemic events. They are especially valuable for use in younger patients.

Since the development of the rapid acting insulin analogues, insulin analogues that supply basal insulin supplementation have been developed. The first long-acting insulin to be made commercially available is insulin glargine. Another long-acting insulin analogue, insulin detemir, is currently in phase IV development. These analogues provide a relatively constant basal insulin supply with no pronounced peak. Long acting insulin analogues cause less hypoglycaemia, especially nocturnal hypoglycaemia in comparison to regular human insulin.