Tags

Type your tag names separated by a space and hit enter

Fast-acting insulin aspart in Japanese patients with type 1 diabetes: Faster onset, higher early exposure and greater early glucose-lowering effect relative to insulin aspart.
J Diabetes Investig 2018; 9(2):303-310JD

Abstract

INTRODUCTION

Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with two added excipients (niacinamide and L-arginine) in order to obtain accelerated absorption after subcutaneous dosing. The present study compared the pharmacokinetic/pharmacodynamic characteristics of faster aspart vs IAsp in Japanese patients with type 1 diabetes.

MATERIALS AND METHODS

In a randomized, double-blind, cross-over design, 43 participants were given faster aspart and IAsp (0.2 U/kg single dose) at two separate dosing visits. Frequent pharmacokinetic blood sampling was carried out, and pharmacodynamics were assessed using an automated euglycemic clamp lasting for a maximum of 12 h after dosing (target 5.5 mmol/L).

RESULTS

Faster aspart showed onset of appearance approximately twice-as-fast vs IAsp (least squares means: 3.0 vs 7.1 min; estimated treatment difference -4.1 min, 95% confidence interval [CI]: -5.0, -3.2; P < 0.001) and onset of action occurring approximately 5 min earlier (20.2 vs 25.5 min; estimated treatment difference -5.3 min, 95% CI: -8.4, -2.2; P = 0.001). Within the first 30 min post-dose, both exposure (area under the curve [AUC]IAsp,0-30 min) and glucose-lowering effect (AUCGIR,0-30 min) were approximately twofold greater for faster aspart vs IAsp (P < 0.001 and P = 0.002, respectively). Bioavailability of faster aspart was similar to IAsp (AUCIAsp,0-t ; estimated treatment ratio 0.99, 90% CI: 0.96-1.02), whereas the total glucose-lowering effect (AUCGIR,0-t) was slightly lower for faster aspart vs IAsp (estimated treatment ratio 0.93, 95% CI: 0.87-0.99, P = 0.020).

CONCLUSIONS

Faster aspart showed faster onset, higher early exposure and a greater early glucose-lowering effect relative to IAsp in Japanese patients with type 1 diabetes, in accordance with previous findings in Caucasian type 1 diabetes patients.

Authors+Show Affiliations

SOUSEIKAI, Hakata Clinic, Fukuoka, Japan.Novo Nordisk Pharma Ltd., Tokyo, Japan.Novo Nordisk A/S, Søborg, Denmark.Novo Nordisk A/S, Søborg, Denmark.

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

28556616

Citation

Shiramoto, Masanari, et al. "Fast-acting Insulin Aspart in Japanese Patients With Type 1 Diabetes: Faster Onset, Higher Early Exposure and Greater Early Glucose-lowering Effect Relative to Insulin Aspart." Journal of Diabetes Investigation, vol. 9, no. 2, 2018, pp. 303-310.
Shiramoto M, Nishida T, Hansen AK, et al. Fast-acting insulin aspart in Japanese patients with type 1 diabetes: Faster onset, higher early exposure and greater early glucose-lowering effect relative to insulin aspart. J Diabetes Investig. 2018;9(2):303-310.
Shiramoto, M., Nishida, T., Hansen, A. K., & Haahr, H. (2018). Fast-acting insulin aspart in Japanese patients with type 1 diabetes: Faster onset, higher early exposure and greater early glucose-lowering effect relative to insulin aspart. Journal of Diabetes Investigation, 9(2), pp. 303-310. doi:10.1111/jdi.12697.
Shiramoto M, et al. Fast-acting Insulin Aspart in Japanese Patients With Type 1 Diabetes: Faster Onset, Higher Early Exposure and Greater Early Glucose-lowering Effect Relative to Insulin Aspart. J Diabetes Investig. 2018;9(2):303-310. PubMed PMID: 28556616.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fast-acting insulin aspart in Japanese patients with type 1 diabetes: Faster onset, higher early exposure and greater early glucose-lowering effect relative to insulin aspart. AU - Shiramoto,Masanari, AU - Nishida,Tomoyuki, AU - Hansen,Ann Kathrine, AU - Haahr,Hanne, Y1 - 2017/07/07/ PY - 2017/01/18/received PY - 2017/05/08/revised PY - 2017/05/22/accepted PY - 2017/5/31/pubmed PY - 2018/8/22/medline PY - 2017/5/31/entrez KW - Japanese KW - Pharmacodynamics KW - Pharmacokinetics SP - 303 EP - 310 JF - Journal of diabetes investigation JO - J Diabetes Investig VL - 9 IS - 2 N2 - INTRODUCTION: Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with two added excipients (niacinamide and L-arginine) in order to obtain accelerated absorption after subcutaneous dosing. The present study compared the pharmacokinetic/pharmacodynamic characteristics of faster aspart vs IAsp in Japanese patients with type 1 diabetes. MATERIALS AND METHODS: In a randomized, double-blind, cross-over design, 43 participants were given faster aspart and IAsp (0.2 U/kg single dose) at two separate dosing visits. Frequent pharmacokinetic blood sampling was carried out, and pharmacodynamics were assessed using an automated euglycemic clamp lasting for a maximum of 12 h after dosing (target 5.5 mmol/L). RESULTS: Faster aspart showed onset of appearance approximately twice-as-fast vs IAsp (least squares means: 3.0 vs 7.1 min; estimated treatment difference -4.1 min, 95% confidence interval [CI]: -5.0, -3.2; P < 0.001) and onset of action occurring approximately 5 min earlier (20.2 vs 25.5 min; estimated treatment difference -5.3 min, 95% CI: -8.4, -2.2; P = 0.001). Within the first 30 min post-dose, both exposure (area under the curve [AUC]IAsp,0-30 min) and glucose-lowering effect (AUCGIR,0-30 min) were approximately twofold greater for faster aspart vs IAsp (P < 0.001 and P = 0.002, respectively). Bioavailability of faster aspart was similar to IAsp (AUCIAsp,0-t ; estimated treatment ratio 0.99, 90% CI: 0.96-1.02), whereas the total glucose-lowering effect (AUCGIR,0-t) was slightly lower for faster aspart vs IAsp (estimated treatment ratio 0.93, 95% CI: 0.87-0.99, P = 0.020). CONCLUSIONS: Faster aspart showed faster onset, higher early exposure and a greater early glucose-lowering effect relative to IAsp in Japanese patients with type 1 diabetes, in accordance with previous findings in Caucasian type 1 diabetes patients. SN - 2040-1124 UR - https://www.unboundmedicine.com/medline/citation/28556616/Fast_acting_insulin_aspart_in_Japanese_patients_with_type_1_diabetes:_Faster_onset_higher_early_exposure_and_greater_early_glucose_lowering_effect_relative_to_insulin_aspart_ L2 - https://doi.org/10.1111/jdi.12697 DB - PRIME DP - Unbound Medicine ER -