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
Masanari Shiramoto, Tomoyuki Nishida, Ann Kathrine Hansen, Hanne Haahr, Masanari Shiramoto, Tomoyuki Nishida, Ann Kathrine Hansen, Hanne Haahr
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.
Keywords: Japanese; Pharmacodynamics; Pharmacokinetics.
© 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
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References
- Wang JS, Tu ST, Lee IT, et al Contribution of postprandial glucose to excess hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring. Diabetes Metab Res Rev. 2011; 27: 79–84.
- Scheen AJ, Schmitt H, Jiang HH, et al Individualizing treatment of type 2 diabetes by targeting postprandial or fasting hyperglycaemia: response to a basal vs a premixed insulin regimen by HbA1c quartiles and ethnicity. Diabetes Metab 2015; 41: 216–222.
- Shimizu H, Uehara Y, Okada S, et al Contribution of fasting and postprandial hyperglycemia to hemoglobin A1c in insulin‐treated Japanese diabetic patients. Endocr J 2008; 55: 753–756.
- Woerle HJ, Neumann C, Zschau S, et al Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes Importance of postprandial glycemia to achieve target HbA1c levels. Diabetes Res Clin Pract 2007; 77: 280–285.
- Fukushima M, Usami M, Ikeda M, et al Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross‐sectional study of Japanese type 2 diabetes. Metabolism 2004; 53: 831–835.
- Horikawa C, Yoshimura Y, Kamada C, et al Dietary intake in Japanese patients with type 2 diabetes: analysis from Japan Diabetes Complications Study. J Diabetes Investig 2014; 5: 176–187.
- Ikeda S, Crawford B, Sato M. Utilization patterns of insulin therapy and healthcare services among Japanese insulin initiators during their first year: a descriptive analysis of administrative hospital data. BMC Health Serv Res 2016; 16: 6.
- Home PD. The pharmacokinetics and pharmacodynamics of rapid‐acting insulin analogues and their clinical consequences. Diabetes Obes Metab 2012; 14: 780–788.
- Home PD. Plasma insulin profiles after subcutaneous injection: how close can we get to physiology in people with diabetes? Diabetes Obes Metab 2015; 17: 1011–1020.
- Buckley ST, Kildegaard J, Høiberg‐Nielsen R, et al Mechanistic analysis into the mode(s) of action of niacinamide in faster‐acting insulin aspart. Diabetes Technol Ther 2016; 18(Suppl 1): A116–A117.
- Heise T, Hövelmann U, Brøndsted L, et al Faster‐acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart. Diabetes Obes Metab 2015; 17: 682–688.
- Heise T, Stender‐Petersen K, Hövelmann U, et al Pharmacokinetic and pharmacodynamic properties of faster‐acting insulin aspart versus insulin aspart across a clinically relevant dose range in subjects with type 1 diabetes mellitus. Clinical Pharmacokinet 2017; 56: 649–660.
- Heise T, Pieber TR, Danne T, et al A pooled analysis of clinical pharmacology trials investigating the pharmacokinetic and pharmacodynamic characteristics of fast‐acting insulin aspart in adults with type 1 diabetes. Clinical Pharmacokinet 2017; 56: 551–559.
- Morello CM. Pharmacokinetics and pharmacodynamics of insulin analogs in special populations with type 2 diabetes mellitus. Int J Gen Med 2011; 4: 827–835.
- Becker RH, Frick AD. Clinical pharmacokinetics and pharmacodynamics of insulin glulisine. Clin Pharmacokinet 2008; 47: 7–20.
- Kaku K, Matsuda M, Urae A, et al Pharmacokinetics and pharmacodynamics of insulin aspart, a rapid‐acting analog of human insulin, in healthy Japanese volunteers. Diabetes Res Clin Pract 2000; 49: 119–126.
- World Medical Association . Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. 59th WMA General Assembly, Seoul, October 2008.
- Ministry of Health and Welfare Ordinance on Good Clinical Practice (MHW Ordinance No. 28). March 27, 1997. Available from: Accessed May 23, 2017. (Japanese)
- American Diabetes Association . Defining and reporting hypoglycaemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycaemia. Diabetes Care 2005; 28: 1245–1249.
- Fieller EC. Some problems in interval estimation. J R Stat Soc Series B Stat Methodol 1954; 16: 175–185.
- European Medicines Agency . Committee for Medicinal Products for Human Use. Guideline on the Investigation of Bioequivalence. CPMP/EWP/QWP/1401/98 Rev. 1/Corr. 20 January 2010. Available from: Accessed May 23, 2017.
- Food and Drug Administration . Code of Federal Regulations. 21 CFR Part 320. Bioavailability and Bioequivalence Requirements. Available from: Accessed May 23, 2017.
- Russell‐Jones D, Bode B, de Block C, et al Fast‐acting insulin aspart improves glycemic control in basal‐bolus treatment for type 1 diabetes: results of a 26‐week multicenter, active‐controlled, treat‐to‐target, randomized, parallel‐group trial (Onset 1). Diabetes Care 2017; 40: 943–950.
- Bowering K, Case C, Harvey J, et al Faster aspart versus insulin aspart as part of a basal‐bolus regimen in inadequately controlled type 2 diabetes: the onset 2 trial. Diabetes Care 2017; 40: 951–957.
Source: PubMed