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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?

SUBMITTER: Pieber TR

PROVIDER: S-EPMC6771872 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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

Pieber Thomas R TR Svehlikova Eva E Brunner Martina M Halberg Inge B IB Due Thomsen Karen Margrete KM Haahr Hanne H

Diabetes, obesity & metabolism 20190610 9

<h4>Aims</h4>To investigate the pharmacokinetic/pharmacodynamic properties of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp) in people with type 2 diabetes (T2D).<h4>Materials and methods</h4>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 hou ...[more]

PMID: 31069935

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Project description:BackgroundFast-acting insulin aspart (faster aspart) is an ultra-fast-acting formulation of insulin aspart (IAsp). This post hoc analysis investigated the pharmacokinetics of faster aspart versus IAsp, measured as free or total IAsp, and the relationship between anti-IAsp antibodies and the pharmacokinetics/pharmacodynamics of faster aspart and IAsp.MethodsFree and total IAsp concentrations and anti-IAsp antibodies were determined in adults with type 1 diabetes mellitus receiving subcutaneous faster aspart and/or IAsp in four single-dose clinical pharmacology trials (n = 175) and a 26-week phase IIIa trial (n = 1040). Pharmacodynamics were assessed by euglycaemic clamp or meal test, respectively.ResultsThe pharmacokinetic profile was left-shifted and early exposure was greater with faster aspart versus IAsp independent of free or total IAsp assay. The faster aspart-IAsp difference in the time to 50% of maximum IAsp concentration in the early part of the pharmacokinetic profile (tEarly 50 % Cmax) [95% confidence interval (CI)] was - 8.8 [- 10.0 to - 7.5] and - 7.6 [- 8.8 to - 6.4] min for free and total IAsp, respectively. The faster aspart/IAsp ratio for the area under the concentration-time curve (AUC) for IAsp from time zero to 30 min (AUCIAsp,0-30 min) [95% CI] was 1.88 [1.74-2.04] and 1.77 [1.64-1.90] for free and total IAsp. Higher anti-IAsp antibody levels were associated with a lower ratio of free/total IAsp for the total AUC for IAsp (AUCIAsp,0-t). Early glucose-lowering effect (AUC for the glucose infusion rate [GIR] from time zero to 60 min [AUCGIR,0-60 min]) was greater by 25-44% for faster aspart versus IAsp independent of anti-IAsp antibody levels. Total glucose-lowering effect (total AUC for GIR [AUCGIR,0-t]) in a clamp and 1-h postprandial glucose increment in a meal test appeared essentially unaffected by anti-IAsp antibodies.ConclusionsFaster aspart provides accelerated pharmacokinetics versus IAsp regardless if based on free or total IAsp assay. Higher anti-IAsp antibodies increase total IAsp concentrations but do not influence faster aspart nor IAsp pharmacodynamics. CLINICALTRIALS.Gov identifiersNCT01618188, NCT02003677, NCT01934712, NCT02568280, NCT01831765.

Dataset Information

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

Publications

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

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