Insulin degludec: A long-acting modern insulin analogue with a predictable pharmacokinetic/ pharmacodynamic profile

摘要

Insulin degludec is, like insulin detemir, a product of coupling of Des-B30 threonine insulin to fatty acid side chains. After injection, degludec self associates, precipitating in subcutaneous tissue. There is a continuous and highly predictable slow dissociation of insulin monomers from this depot; insulin levels rise immediately reaching tmax at 10-12 hours, followed by a slow decline with a t1/2 of 17-21 hours, roughly double the duration of action of insulin glargine. An important property of degludec not shared by glargine is miscibility with rapid-acting insulin. Although the effect of coadministered insulin aspart is somewhat blunted by coformulation with degludec, a preparation of 70% degludec and 30% aspart has predictable pharmacodynamics. Daily administration of degludec has glucose-lowering benefits not different from those of glargine, with purportedly less hypoglycemia. Although degludec is approved and marketed in Europe under the brand name Tresiba?, the U.S. Food and Drug Administration, in a surprising development, challenged the assertion of lower tendency to hypoglycemia with degludec, and, more importantly, raised concerns that degludec may have a higher cardiovascular risk than glargine. Only a long-term study in a large patient population can resolve these questions. However, release of degludec for marketing to appropriate patients should proceed while awaiting the results of such a study.