Greater early postprandial suppression of endogenous glucose production and higher initial glucose disappearance is achieved with fast‐acting insulin aspart compared with insulin aspart |
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| Authors: | Ananda Basu MD Thomas R. Pieber MD Ann K. Hansen PhD Stefanie Sach‐Friedl MSc Lars Erichsen PhD Rita Basu MD Hanne Haahr PhD |
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| Affiliation: | 1. Division of Endocrinology, University of Virginia, Charlottesville, Virginia;2. Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria;3. Novo Nordisk, S?borg, Denmark |
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| Abstract: | Aim To investigate the mechanisms behind the lower postprandial glucose (PPG) concentrations achieved with fast‐acting insulin aspart (faster aspart) than with insulin aspart (IAsp). Materials and methods In a randomized, double‐blind, crossover trial, 41 people with type 1 diabetes received identical subcutaneous single faster aspart and IAsp doses (individualized for each participant), together with a standardized mixed meal (including 75 g carbohydrate labelled with [1‐13C] glucose). PPG turnover was determined by the triple‐tracer meal method using continuous, variable [6‐3H] glucose and [6,6‐2H2] glucose infusion. Results Insulin exposure within the first hour was 32% greater with faster aspart than with IAsp (treatment ratio faster aspart/IAsp 1.32 [95% confidence interval {CI} 1.18;1.48]; P < .001), leading to a 0.59‐mmol/L non‐significantly smaller PPG increment at 1 hour (ΔPG1h; treatment difference faster aspart–IAsp ?0.59 mmol/L [95% CI –1.19; 0.01]; P = .055). The trend towards reduced ΔPG1h with faster aspart was attributable to 12% greater suppression of endogenous glucose production (EGP; treatment ratio 1.12 [95% CI 1.01; 1.25]; P = .040) and 23% higher glucose disappearance (1.23 [95% CI 1.05; 1.45]; P = .012) with faster aspart than with IAsp during the first hour. Suppression of free fatty acid levels during the first hour was 36% greater for faster aspart than for IAsp (1.36 [95% CI 1.01;1.88]; P = .042). Conclusions The trend towards improved PPG control with faster aspart vs IAsp in this study was attributable to both greater early suppression of EGP and stimulation of glucose disappearance. |
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| Keywords: | glucose metabolism insulin therapy pharmacodynamics pharmacokinetics type 1 diabetes type 2 diabetes |
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