New Insulins and Insulin Therapy

Abstract

While the pharmacokinetic properties of the long-acting insulin analogues, insulin glargine and insulin detemir, clearly demonstrate clinical benefits over NPH insulin in terms of reduced frequency of overall and nocturnal hypoglycaemic events and lowered glycaemic variability, several new insulin analogues with even longer and smoother time-action profiles are being developed and explored. Among these, insulin degludec is the first to enter the market. The ultra-long action profile of this insulin analogue is mainly the result of a slow and stable release of insulin degludec monomers from soluble multihexamers that form after subcutaneous administration. In the last year, the results of the first phase II trials with insulin degludec have been published, where the efficacy and safety of this basal insulin analogue have been compared with insulin glargine in patients with type 1 (T1D) and type 2 (T2D) diabetes. With regard to short-acting insulins for mealtime insulin supplementation, there is also a search for new insulins with a more rapid onset of action, and hence improved postprandial glucose control. Linjeta (formerly named VIAject) is a human insulin formulation with faster insulin absorption and action than insulin lispro and regular human insulin. A new drug application to market Linjeta as a treatment for diabetes was submitted to the US Food and Drug Administration (FDA) by the manufacturer at the beginning of 2010. However, the FDA’s review cycle, which was announced late in 2010, concluded that the application could not be approved in its present form. The FDA’s complete response letter included comments related to clinical trials, statistical analysis and chemistry, manufacturing and controls. The FDA requested that the company should conduct two new phase III clinical trials using the commercial formulation, one in patients with T1D and the other in patients with T2D, to establish efficacy and safety with regard to hypoglycaemia and toleration. Co-administration of hyaluronidase together with insulin is another novel concept which has been proven to accelerate the absorption of both insulin lispro and regular human insulin in healthy subjects. In this review, we comment on two recent publications in which the pharmacokinetic and pharmacodynamic characteristics of Linjeta and co-formulations of prandial insulins with recombinant human hyaluronidase were investigated in patients with T1D. Lastly, a recent review on the ongoing discussion regarding insulin treatment and cancer risk is included.