Pharmacokinetics of Faster and Standard Insulin Aspart During Fully Closed-Loop Insulin Delivery in Type 2 Diabetes.

Herzig, David; Dehais, Joachim; Prost, Jean-Christophe; Nakas, Christos T.; Stettler, Christoph; Bally, Lia; Hovorka, Roman (2020). Pharmacokinetics of Faster and Standard Insulin Aspart During Fully Closed-Loop Insulin Delivery in Type 2 Diabetes. Diabetes technology & therapeutics, 22(9), pp. 691-696. Mary Ann Liebert 10.1089/dia.2019.0477

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Background:
Faster insulin aspart is a novel formulation of insulin aspart aiming to accelerate its subcutaneous absorption. The aim of this study was to compare pharmacokinetics of faster insulin aspart versus standard insulin aspart in adults with type 2 diabetes during closed-loop insulin delivery.
Methods:
We assessed the pharmacokinetics of faster and standard insulin aspart from data obtained in a randomized double-blind crossover study evaluating fully closed-loop insulin delivery in adults with type 2 diabetes (n = 13, age 59 ± 10 years, BMI 34.5 ± 9.1 kg/m2, HbA1c 7.7% ± 1.2% [60 ± 13 mmol/mol]). Blood samples were collected every 15-30 min for 10 h to determine plasma insulin aspart concentration using liquid chromatography mass spectrometry. Time to peak plasma concentration (Tmax) was calculated using a two-compartment model.
Results:
Tmax was 68.7 ± 21.6 min for faster aspart and 89.7 ± 31.8 min for aspart (mean paired difference faster aspart minus aspart -15.5 min, 95% CI [-31.6 to 0.6 min], P = 0.06). Metabolic clearance rate did not differ between the two insulins (P = 0.61). Insulin amount delivered during closed-loop with faster aspart positively correlated with Tmax (rS = 0.73, P = 0.01), whereas no statistically significant correlation was found with body mass index (BMI), weight or HbA1C (all P > 0.18).
Conclusion:
In conclusion, Tmax tended to be shorter for faster aspart versus aspart during fully automated closed-loop insulin delivery and positively correlated with the amount of insulin delivered.

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