Abstract
AimsTo investigate the pharmacokinetic/pharmacodynamic properties of fast‐acting insulin aspart (faster aspart) versus insulin aspart (IAsp) in people with type 2 diabetes (T2D).Materials and methodsIn a randomized, double‐blind, crossover design, 61 people with T2D usually treated with insulin ± oral antidiabetic drug(s) received single‐dose faster aspart and IAsp (0.3 U/kg) on separate visits. Blood samples for pharmacokinetic assessment were collected frequently until 12 hours post‐dose. Glucose‐lowering effect was determined in a euglycaemic clamp lasting up to 12 hours post‐dose (target 5.0 mmol/L).ResultsThe serum IAsp pharmacokinetic profile and glucose‐lowering effect profile were shifted to the left for faster aspart versus IAsp. Least squares mean (± SE) onset of appearance was 3.3 ± 0.3 minutes for faster aspart, which was 1.2 minutes earlier than for IAsp (95% confidence interval [CI] −1.8;−0.5; P = .001). Onset of action for faster aspart was 8.9 minutes earlier (95% CI −12.1;−5.7; P < .001) than for IAsp. During the first 30 minutes after dosing, 89% larger IAsp exposure (ratio faster aspart/IAsp 1.89 [95% CI 1.56;2.28]; P < .001) and 147% greater glucose‐lowering effect (2.47 [95% CI 1.58;6.22]; P < .001) were observed for faster aspart compared with IAsp. Offset of exposure (time to 50% of maximum IAsp concentration in the late part of the pharmacokinetic profile) occurred earlier for faster aspart (difference faster aspart – IAsp −36.4 minutes [95% CI −55.3;−17.6]; P < .001). The treatment difference of faster aspart – IAsp in offset of glucose‐lowering effect (time to 50% of maximum glucose infusion rate in the late part of the glucose infusion rate profile) was −14.4 minutes (95% CI −34.4;5.5; P = .152).ConclusionsIn people with T2D, faster aspart was associated with earlier onset and greater initial exposure and glucose‐lowering effect compared with IAsp, as previously shown in people with type 1 diabetes.
Highlights
Fast-acting insulin aspart is a novel insulin aspart (IAsp) formulation with two additional excipients: L-arginine to ensure a stable formulation and niacinamide to provide increased early absorption after subcutaneous dosing[1]; faster aspart is an insulin with ultrafast action to enable improved postprandial glycaemic control compared to that obtained with previously developed rapid-acting insulin products.[2,3] In people with type 1 diabetes (T1D), faster aspart has an accelerated onset of appearance and an up to twofold larger initial insulin exposure and glucose-lowering effect compared with IAsp.[4-7]
The sample size calculation was based on a comparison of the primary endpoint between faster aspart and IAsp in particpants with type 2 diabetes (T2D), using information for an earlier faster aspart formulation from a previous trial that included both participants with T1D and T2D.13
The main findings were that the serum IAsp pharmacokinetic profile, the glucose-lowering effect profile and the free fatty acid (FFA) profile were all left-shifted for faster aspart versus IAsp
Summary
Fast-acting insulin aspart (faster aspart) is a novel insulin aspart (IAsp) formulation with two additional excipients: L-arginine to ensure a stable formulation and niacinamide to provide increased early absorption after subcutaneous dosing[1]; faster aspart is an insulin with ultrafast action to enable improved postprandial glycaemic control compared to that obtained with previously developed rapid-acting insulin products.[2,3] In people with type 1 diabetes (T1D), faster aspart has an accelerated onset of appearance and an up to twofold larger initial insulin exposure and glucose-lowering effect compared with IAsp.[4-7]. In people with type 1 diabetes (T1D), faster aspart has an accelerated onset of appearance and an up to twofold larger initial insulin exposure and glucose-lowering effect compared with IAsp.[4-7]. The pharmacokinetic/pharmacodynamic properties of faster aspart have not been investigated in people with type 2 diabetes (T2D). When oral antidiabetic drugs (OADs) alone or in combination with glucagon-like peptide-1 receptor agonists are no longer sufficient to achieve or maintain glycaemic control, current diabetes guidelines recommend the addition of basal insulin.[8]. Treatment can be further intensified by the addition of mealtime insulin in a basal-bolus regimen to address postprandial glucose control.[8]. The aim of the present study, was to investigate the pharmacokinetic/pharmacodynamic characteristics of faster aspart versus IAsp for the first time in people with T2D
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