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

Abstract

Aims To 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 methods In 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). Results The 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). Conclusions In 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.

Short‐term fully closed‐loop insulin delivery using faster insulin aspart compared with standard insulin aspart in type 2 diabetes

“…Previous trials that evaluated the use of faster versus standard insulin aspart with injection and pump therapy reported no significant differences for overall glycaemic control between the two insulin formulations . Several factors may explain the lack of improved glucose control during short‐term application of fully closed‐loop despite the more favourable pharmacokinetic and pharmacodynamic profile of faster insulin aspart 2 that has also recently been confirmed in adults with type 2 diabetes . First, the adaptation of the fully closed‐loop control algorithm to higher insulin doses needed with faster insulin aspart, which may in part be related to the left‐shift of the pharmacokinetic profile, may take longer and the short study duration was not permissive for this to happen.…”

“…First, the adaptation of the fully closed‐loop control algorithm to higher insulin doses needed with faster insulin aspart, which may in part be related to the left‐shift of the pharmacokinetic profile, may take longer and the short study duration was not permissive for this to happen. Second, the difference in the onset of action, 8.9 minutes earlier, is modest, especially in the light of the considerable intra‐patient variability in insulin absorption, thereby diminishing potential benefits. Thus, further longer and adequately powered studies are warranted.…”

“…The more favourable pharmacokinetic and pharmacodynamic properties of faster insulin aspart compared with standard insulin aspart were substantiated in clinical studies enrolling people with type 1 and type 2 diabetes …”

Fast-Acting Insulin Aspart: A Review of its Pharmacokinetic and Pharmacodynamic Properties and the Clinical Consequences

“…This review includes 12 clinical pharmacology trials [16][17][18][19][20][21][22][23][24][25][26][27] and 10 other clinical trials (most of them part of the Onset phase III clinical development programme) [28-35, 42, 43] with faster aspart, identified by PubMed searches for the terms 'faster aspart clinical trial' and 'faster acting insulin aspart onset', as well as a ClinicalTrials.gov search for phase I trials using the term 'faster aspart'. To be included in this review, it was required that trials had been published in article form, however with two exceptions, where inclusion was assessed highly relevant for the completeness of the review [27,33].…”

“…Figure 1 shows a conceptual model based on clinical pharmacokinetic data describing how the rate of absorption depends on varying concentrations of niacinamide and zinc in the faster aspart formulation. Several faster aspart formulations with different combinations of niacinamide and zinc concentrations were tested in a clinical pharmacology trial, and, [16][17][18][19][20][21][22][23][24][25][26][27]. Moreover, phase III trials have investigated the efficacy and safety of faster aspart versus IAsp in subjects with T1D or T2D [28][29][30][31][32][33][34][35].…”