Pharmacological properties of faster-acting insulin aspart vs insulin aspart in patients with type 1 diabetes receiving continuous subcutaneous insulin infusion: A randomized, double-blind, crossover trial
Tim Heise, Eric Zijlstra, Leszek Nosek, Tord Rikte, Hanne Haahr, Tim Heise, Eric Zijlstra, Leszek Nosek, Tord Rikte, Hanne Haahr
Abstract
Aim: To evaluate the pharmacological characteristics of faster-acting insulin aspart (faster aspart) compared with insulin aspart (IAsp) during continuous subcutaneous insulin infusion (CSII).
Methods: In this randomized, double-blind, crossover trial, 48 men and women aged 18 to 64 years with type 1 diabetes mellitus (T1DM) received faster aspart and IAsp as a 0.15 U/kg bolus dose via CSII, on top of a basal rate (0.02 U/kg/h), in a glucose clamp setting (target 5.5 mmol/L).
Results: After a CSII bolus dose, the pharmacokinetic/pharmacodynamic profiles for faster aspart were left-shifted compared with those for IAsp. For faster aspart vs IAsp, the early glucose-lowering effect (area under the curve for glucose infusion rate [GIR]0-30min ) was approximately 2-fold higher (least squares means 24.9 vs 11.4 mg/kg; estimated ratio faster aspart/IAsp 2.18, 95% confidence interval [CI] [1.33; 5.04]; P = .002), onset of glucose-lowering effect (time to early 50% of maximum GIR) occurred 11.1 minutes earlier (41.1 vs 52.3 minutes; 95% CI faster aspart - IAsp [-15.4; -6.9]; P<.001), and offset of glucose-lowering effect (time to late 50% of maximum GIR) occurred 24.0 minutes earlier (214.7 vs 238.7 minutes; 95% CI [-38.9; -9.1]; P=.002). Likewise, significantly greater early exposure and significantly earlier onset and offset of exposure were observed for faster aspart vs IAsp. Faster aspart and IAsp were both well tolerated.
Conclusions: In patients with T1DM using CSII, faster aspart better mimics the endogenous prandial insulin secretion and action than does IAsp. Faster aspart therefore has the potential to provide clinical benefits over current rapid-acting insulins in the insulin pump setting.
Keywords: insulin pump therapy; pharmacodynamics; pharmacokinetics; type 1 diabetes.
© 2016 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
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References
- 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.
- Home PD. The pharmacokinetics and pharmacodynamics of rapid‐acting insulin analogues and their clinical consequences. Diabetes Obes Metab. 2012;14:780‐788.
- Hermansen K, Bohl M, Schioldan AG. Insulin aspart in the management of diabetes mellitus: 15 years of clinical experience. Drugs. 2016;76:41‐74.
- Kalra S, Gupta Y. Ultra‐fast acting insulin analogues. Recent Pat Endocr Metab Immune Drug Discov. 2014;8:117‐123.
- Heinemann L, Muchmore DB. Ultrafast‐acting insulins: state of the art. J Diabetes Sci Technol. 2012;6:728‐742.
- Pozzilli P, Battelino T, Danne T, Hovorka R, Jarosz‐Chobot P, Renard E. Continuous subcutaneous insulin infusion in diabetes: patient populations, safety, efficacy, and pharmacoeconomics. Diabetes Metab Res Rev. 2016;32:21‐39.
- Thabit H, Hovorka R. Continuous subcutaneous insulin infusion therapy and multiple daily insulin injections in type 1 diabetes mellitus: a comparative overview and future horizons. Expert Opin Drug Deliv. 2016;13:389‐400.
- Yeh HC, Brown TT, Maruthur N, et al. Comparative effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus: a systematic review and meta‐analysis. Ann Intern Med. 2012;157:336‐347.
- Cengiz E, Bode B, Van Name M, Tamborlane WV. Moving toward the ideal insulin for insulin pumps. Expert Rev Med Devices. 2016;13:57‐69.
- Food and Drug Administration . Inactive ingredient search for approved drug products. . Accessed October 21, 2016.
- Heise T, Hövelmann U, Brøndsted L, Adrian CL, Nosek L, Haahr H. 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.
- Radermecker RP, Scheen AJ. Continuous subcutaneous insulin infusion with short‐acting insulin analogues or human regular insulin: efficacy, safety, quality of life, and cost‐effectiveness. Diabetes Metab Res Rev. 2004;20:178‐188.
- Bode BW. Comparison of pharmacokinetic properties, physicochemical stability, and pump compatibility of 3 rapid‐acting insulin analogues‐aspart, lispro and glulisine. Endocr Pract. 2011;17:271‐280.
- Benesch C, Heise T, Klein O, Heinemann L, Arnolds S. How to assess the quality of glucose clamps? Evaluation of clamps performed with ClampArt, a novel automated clamp device. J Diabetes Sci Technol. 2015;9:792‐800.
- 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.
- Bode B, Hyveled L, Tamer SC, Ybanez P, Demissie M. Improved postprandial glycemic control with faster‐acting insulin aspart in subjects with type 1 diabetes using CSII. Diabetes. 2015;64(suppl 1):A253 (Poster 994‐P).
- Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care. 2003;26:881‐885.
- 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.
- Riddle M, Umpierrez G, DiGenio A, Zhou R, Rosenstock J. Contributions of basal and postprandial hyperglycemia over a wide range of A1C levels before and after treatment intensification in type 2 diabetes. Diabetes Care. 2011;34:2508‐2514.
- Russell‐Jones D, Bode B, de Block C, et al. Double‐blind mealtime faster‐acting insulin aspart vs insulin aspart in basal–bolus improves glycemic control in T1D: the onset® 1 trial. Diabetes. 2016;65(suppl 1):A77.
- Cengiz E. Closer to ideal insulin action: ultra fast acting insulins. Panminerva Med. 2013;55:269‐275.
- Maahs DM, Horton LA, Chase HP. The use of insulin pumps in youth with type 1 diabetes. Diabetes Technol Ther. 2010;12:S59‐S65.
- Heise T, Haahr H, Jensen L, Erichsen L, Hompesch M. Faster‐acting insulin aspart improves postprandial glycemia vs insulin aspart in patients with type 1 diabetes mellitus (T1DM). Diabetes. 2014;63(suppl 1):A34.
- Bell KJ, Smart CE, Steil GM, Brand‐Miller JC, King B, Wolpert HA. Impact of fat, protein, and glycemic index on postprandial glucose control in type 1 diabetes: implications for intensive diabetes management in the continuous glucose monitoring era. Diabetes Care. 2015;38:1008‐1015.
- 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.
- Regittnig W, Urschitz M, Lehki B, et al. Absorption kinetics of insulin following subcutaneous bolus administration with different bolus durations. Diabetes. 2013;62(suppl 1):A247 (Poster 966‐P).
- Jain L, Parks MH, Sahajwalla C. Determination of time to onset and rate of action of insulin products: importance and new approaches. J Pharm Sci. 2013;102:271‐279.
- Swinnen SG, Holleman F, DeVries JH. The interpretation of glucose clamp studies of long‐acting insulin analogues: from physiology to marketing and back. Diabetologia. 2008;51:1790‐1795.
Source: PubMed