Insulin Aspart in the Management of Diabetes Mellitus: 15 Years of Clinical Experience

Abstract

Limiting excessive postprandial glucose excursions is an important component of good overall glycemic control in diabetes mellitus. Pharmacokinetic studies have shown that insulin aspart, which is structurally identical to regular human insulin except for the replacement of a single proline amino acid with an aspartic acid residue, has a more physiologic time-action profile (i.e., reaches a higher peak and reaches that peak sooner) than regular human insulin. As expected with this improved pharmacokinetic profile, insulin aspart demonstrates a greater glucose-lowering effect compared with regular human insulin. Numerous randomized controlled trials and a meta-analysis have also demonstrated improved postprandial control with insulin aspart compared with regular human insulin in patients with type 1 or type 2 diabetes, as well as efficacy and safety in children, pregnant patients, hospitalized patients, and patients using continuous subcutaneous insulin infusion. Studies have demonstrated that step-wise addition of insulin aspart is a viable intensification option for patients with type 2 diabetes failing on basal insulin. Insulin aspart has shown a good safety profile, with no evidence of increased receptor binding, mitogenicity, stimulation of anti-insulin antibodies, or hypoglycemia compared with regular human insulin. In one meta-analysis, there was evidence of a lower rate of nocturnal hypoglycemia compared with regular human insulin and, in a trial that specifically included patients with a history of recurrent hypoglycemia, a significantly lower rate of severe hypoglycemic episodes. The next generation of insulin aspart (faster-acting insulin aspart) is being developed with a view to further improving on these pharmacokinetic/pharmacodynamic properties.

Fig. 1

Pharmacokinetics of insulin aspart compared with soluble/regular human insulin in a healthy volunteers (n = 19), b patients with T1D (n = 22) and c people with T2D (n = 37). C _max maximum concentration, SD standard deviation, t time, T1D type 1 diabetes, T2D type 2 diabetes, T _max maximum time. a Reproduced with kind permission from Springer Science + Business Media: Home et al. [39]. b Reproduced with permission from American Diabetes Association. Diabetes Care, American Diabetes Association, 1999. Copyright and all rights reserved. Material from this publication has been used with the permission of American Diabetes Association [41]. c Reproduced with permission from Perriello et al. [44], copyright © 2005 John Wiley & Sons, Inc.