The association between anti-insulin aspart antibodies and the pharmacokinetic and pharmacodynamic characteristics of fast-acting insulin aspart in children and adolescents with type 1 diabetes.
Pediatr Diabetes. 2020 Apr 19;:
Authors: Biester T, Von Dem Berge T, Bendtsen LQ, Bendtsen MD, Rathor N, Danne T, Haahr H
BACKGROUND: Fast-acting insulin aspart (faster aspart) is a novel formulation of insulin aspart (IAsp) ensuring ultra-fast absorption and effect.
AIM: To compare the pharmacokinetics between faster aspart and IAsp, based on free or total IAsp measurement, and investigate the association between anti-IAsp antibodies and faster aspart and IAsp pharmacological properties in children and adolescents with type 1 diabetes (T1D).
METHODS: In a randomized, two-period crossover trial, 12 children, 16 adolescents and 15 adults (6-11, 12-17 and 18-64 years) received 0.2 U/kg double-blind single-dose subcutaneous faster aspart or IAsp followed by a standardized liquid meal test.
RESULTS: Across age groups, the pharmacokinetic profile was left-shifted including greater early exposure for faster aspart vs IAsp irrespective of free or total IAsp assay. Onset of appearance occurred 2.4-5.0 min (free) or 1.8-3.0 min (total) earlier for faster aspart vs IAsp (P < 0.05). Treatment ratios (faster aspart/IAsp) for 0-30 min IAsp exposure were 1.60-2.11 and 1.62-1.96, respectively (children, free: P = 0.062; otherwise P < 0.05). The ratio of free/total IAsp for overall exposure (AUCIAsp,0-t ) was negatively associated with anti-IAsp antibody level across age. Pooling with a previous similar trial showed no clear association between anti-IAsp antibodies and meal test 1-hour or 2-hour postprandial glucose increment independent of age and insulin treatment (R2 ≤ 0.070; P ≥ 0.17).
CONCLUSION: In children and adolescents with T1D, faster aspart provides ultra-fast pharmacokinetics irrespective of free or total IAsp assay. Elevated anti-IAsp antibodies are associated with higher total IAsp concentration, but do not impact faster aspart and IAsp glucose-lowering effect. ClinicalTrials.gov IDs: NCT03407599 and NCT02035371. This article is protected by copyright. All rights reserved.
PMID: 32306477 [PubMed – as supplied by publisher]