A Comparison of Pharmacokinetic and Pharmacodynamic Properties Between Faster-Acting Insulin Aspart and Insulin Aspart in Elderly Subjects with Type 1 Diabetes Mellitus

Abstract

BackgroundDue to population aging, an increasing number of elderly patients with diabetes use insulin. It is therefore important to investigate the characteristics of new insulins in this population. Faster-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with faster absorption. This study investigated the pharmacological properties of faster aspart in elderly subjects with type 1 diabetes mellitus (T1DM).MethodsIn a randomised, double-blind, two-period crossover trial, 30 elderly (≥65 years) and 37 younger adults (18–35 years) with T1DM received single subcutaneous faster aspart or IAsp dosing (0.2 U/kg) and underwent an euglycaemic clamp (target 5.5 mmol/L) for up to 12 h.ResultsThe pharmacokinetic and pharmacodynamic time profiles were left-shifted for faster aspart versus IAsp. In each age group, onset of appearance occurred approximately twice as fast (~3 min earlier) and early exposure (area under the concentration–time curve [AUC] for serum IAsp from time zero to 30 min [AUCIAsp,0-30 min]) was greater (by 86% in elderly and 67% in younger adults) for faster aspart than for IAsp. Likewise, onset of action occurred 10 min faster in the elderly and 9 min faster in younger adults, and early glucose-lowering effect (AUC for the glucose infusion rate [GIR] from time zero to 30 min [AUCGIR,0-30 min]) was greater (by 109%) for faster aspart than for IAsp in both age groups. Total exposure (AUCIAsp,0-t) and the maximum concentration (C max) for faster aspart were greater (by 30 and 28%, respectively) in elderly than in younger adults. No age group differences were seen for the total (AUCGIR,0-t) or maximum (GIRmax) glucose-lowering effect.ConclusionThis study demonstrated that the ultra-fast pharmacological properties of faster aspart are similar in elderly subjects and younger adults with T1DM. ClinicalTrials.gov Identifier: NCT02003677.Electronic supplementary materialThe online version of this article (doi:10.1007/s40266-016-0418-6) contains supplementary material, which is available to authorized users.

Fast‐acting insulin aspart in people with type 2 diabetes: Earlier onset and greater initial exposure and glucose‐lowering effect compared with insulin aspart

“…Cmax , onset of action and t Early 50% GIRmax for faster aspart in the present study in people with T2D are similar to those seen in people with T1D. 5,6,15 This indicates that the pharmacological characteristics of faster aspart immediately after dose administration are independent of type of diabetes.…”

“…The majority of AEs were mild in intensity and assessed as unlikely to be related to T A B L E 1 Onset of exposure and onset of glucose-lowering effect for fast-acting insulin aspart versus insulin aspart in people with type 2 diabetes The overall left-shift of the pharmacokinetic/pharmacodynamic profiles with faster aspart versus IAsp in the present study in participants with T2D was comparable to that seen in people with T1D. 5,6,15 It has been reported that the absorption kinetics of human insulin are slower in people with T2D than in those with T1D 10,16 ; therefore, it is interesting that absolute values for onset of appearance, t Early 50%…”

“…The overall left‐shift of the pharmacokinetic/pharmacodynamic profiles with faster aspart versus IAsp in the present study in participants with T2D was comparable to that seen in people with T1D . It has been reported that the absorption kinetics of human insulin are slower in people with T2D than in those with T1D; therefore, it is interesting that absolute values for onset of appearance, t Early 50% Cmax , onset of action and t Early 50% GIRmax for faster aspart in the present study in people with T2D are similar to those seen in people with T1D . This indicates that the pharmacological characteristics of faster aspart immediately after dose administration are independent of type of diabetes.…”

Use of fast‐acting insulin aspart in insulin pump therapy in clinical practice

“…In addition, offset of exposure and glucose‐lowering effect occurred 12–14 minutes earlier with faster aspart than with IAsp. Similar pharmacological properties following subcutaneous injection have been observed in elderly adults and in a Japanese population, as well as in children and adolescents with T1D …”

Development of glucose-responsive ‘smart’ insulin systems

“…Development of novel insulin analogs with more rapid onset of activity and shorter duration of action (relative to current insulin analog products Humalog ® , Novolog ® , and Apidra ® (40-42)) could improve closed-loop systems by providing more predicable pharmacodynamic profiles and hence more accurate calculation of insulin doses. Examples of more rapid formulations are provided by Novolog-based FIAsp (a reformulation of insulin aspart to contain excepients that promote capillary absorption) or addition of the degradative enzyme hyaluronidase to wild-type insulin (rHuPH20; Halozyme, Inc.) (43, 44*, 45*); the latter approach is no longer being pursued.…”