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Fast-acting insulin aspart in people with type 2 diabetes: Earlier onset and greater initial exposure and glucose-lowering effect compared with insulin aspart.
Diabetes Obes Metab 2019; 21(9):2068-2075DO

Abstract

AIMS

To investigate the pharmacokinetic/pharmacodynamic properties of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp) in people with type 2 diabetes (T2D).

MATERIALS AND METHODS

In a randomized, double-blind, crossover design, 61 people with T2D usually treated with insulin ± oral antidiabetic drug(s) received single-dose faster aspart and IAsp (0.3 U/kg) on separate visits. Blood samples for pharmacokinetic assessment were collected frequently until 12 hours post-dose. Glucose-lowering effect was determined in a euglycaemic clamp lasting up to 12 hours post-dose (target 5.0 mmol/L).

RESULTS

The serum IAsp pharmacokinetic profile and glucose-lowering effect profile were shifted to the left for faster aspart versus IAsp. Least squares mean (± SE) onset of appearance was 3.3 ± 0.3 minutes for faster aspart, which was 1.2 minutes earlier than for IAsp (95% confidence interval [CI] -1.8;-0.5; P = .001). Onset of action for faster aspart was 8.9 minutes earlier (95% CI -12.1;-5.7; P < .001) than for IAsp. During the first 30 minutes after dosing, 89% larger IAsp exposure (ratio faster aspart/IAsp 1.89 [95% CI 1.56;2.28]; P < .001) and 147% greater glucose-lowering effect (2.47 [95% CI 1.58;6.22]; P < .001) were observed for faster aspart compared with IAsp. Offset of exposure (time to 50% of maximum IAsp concentration in the late part of the pharmacokinetic profile) occurred earlier for faster aspart (difference faster aspart - IAsp -36.4 minutes [95% CI -55.3;-17.6]; P < .001). The treatment difference of faster aspart - IAsp in offset of glucose-lowering effect (time to 50% of maximum glucose infusion rate in the late part of the glucose infusion rate profile) was -14.4 minutes (95% CI -34.4;5.5; P = .152).

CONCLUSIONS

In people with T2D, faster aspart was associated with earlier onset and greater initial exposure and glucose-lowering effect compared with IAsp, as previously shown in people with type 1 diabetes.

Authors+Show Affiliations

Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.CF Clinical Research Center, Center for Medical Research, Medical University of Graz, Graz, Austria.Novo Nordisk, Søborg, Denmark.Novo Nordisk, Aalborg, Denmark.Novo Nordisk, Søborg, Denmark.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31069935

Citation

Pieber, Thomas R., et al. "Fast-acting Insulin Aspart in People With Type 2 Diabetes: Earlier Onset and Greater Initial Exposure and Glucose-lowering Effect Compared With Insulin Aspart." Diabetes, Obesity & Metabolism, vol. 21, no. 9, 2019, pp. 2068-2075.
Pieber TR, Svehlikova E, Brunner M, et al. Fast-acting insulin aspart in people with type 2 diabetes: Earlier onset and greater initial exposure and glucose-lowering effect compared with insulin aspart. Diabetes Obes Metab. 2019;21(9):2068-2075.
Pieber, T. R., Svehlikova, E., Brunner, M., Halberg, I. B., Due Thomsen, K. M., & Haahr, H. (2019). Fast-acting insulin aspart in people with type 2 diabetes: Earlier onset and greater initial exposure and glucose-lowering effect compared with insulin aspart. Diabetes, Obesity & Metabolism, 21(9), pp. 2068-2075. doi:10.1111/dom.13767.
Pieber TR, et al. Fast-acting Insulin Aspart in People With Type 2 Diabetes: Earlier Onset and Greater Initial Exposure and Glucose-lowering Effect Compared With Insulin Aspart. Diabetes Obes Metab. 2019;21(9):2068-2075. PubMed PMID: 31069935.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fast-acting insulin aspart in people with type 2 diabetes: Earlier onset and greater initial exposure and glucose-lowering effect compared with insulin aspart. AU - Pieber,Thomas R, AU - Svehlikova,Eva, AU - Brunner,Martina, AU - Halberg,Inge B, AU - Due Thomsen,Karen Margrete, AU - Haahr,Hanne, Y1 - 2019/06/10/ PY - 2019/04/08/received PY - 2019/05/03/revised PY - 2019/05/05/accepted PY - 2019/5/10/pubmed PY - 2019/5/10/medline PY - 2019/5/10/entrez KW - clinical trial KW - insulin therapy KW - pharmacodynamics KW - pharmacokinetics KW - phase I-II study KW - type 2 diabetes SP - 2068 EP - 2075 JF - Diabetes, obesity & metabolism JO - Diabetes Obes Metab VL - 21 IS - 9 N2 - AIMS: To investigate the pharmacokinetic/pharmacodynamic properties of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp) in people with type 2 diabetes (T2D). MATERIALS AND METHODS: In a randomized, double-blind, crossover design, 61 people with T2D usually treated with insulin ± oral antidiabetic drug(s) received single-dose faster aspart and IAsp (0.3 U/kg) on separate visits. Blood samples for pharmacokinetic assessment were collected frequently until 12 hours post-dose. Glucose-lowering effect was determined in a euglycaemic clamp lasting up to 12 hours post-dose (target 5.0 mmol/L). RESULTS: The serum IAsp pharmacokinetic profile and glucose-lowering effect profile were shifted to the left for faster aspart versus IAsp. Least squares mean (± SE) onset of appearance was 3.3 ± 0.3 minutes for faster aspart, which was 1.2 minutes earlier than for IAsp (95% confidence interval [CI] -1.8;-0.5; P = .001). Onset of action for faster aspart was 8.9 minutes earlier (95% CI -12.1;-5.7; P < .001) than for IAsp. During the first 30 minutes after dosing, 89% larger IAsp exposure (ratio faster aspart/IAsp 1.89 [95% CI 1.56;2.28]; P < .001) and 147% greater glucose-lowering effect (2.47 [95% CI 1.58;6.22]; P < .001) were observed for faster aspart compared with IAsp. Offset of exposure (time to 50% of maximum IAsp concentration in the late part of the pharmacokinetic profile) occurred earlier for faster aspart (difference faster aspart - IAsp -36.4 minutes [95% CI -55.3;-17.6]; P < .001). The treatment difference of faster aspart - IAsp in offset of glucose-lowering effect (time to 50% of maximum glucose infusion rate in the late part of the glucose infusion rate profile) was -14.4 minutes (95% CI -34.4;5.5; P = .152). CONCLUSIONS: In people with T2D, faster aspart was associated with earlier onset and greater initial exposure and glucose-lowering effect compared with IAsp, as previously shown in people with type 1 diabetes. SN - 1463-1326 UR - https://www.unboundmedicine.com/medline/citation/31069935/Fast_acting_insulin_aspart_in_people_with_type_2_diabetes:_Earlier_onset_and_greater_initial_exposure_and_glucose_lowering_effect_compared_with_insulin_aspart_ L2 - https://doi.org/10.1111/dom.13767 DB - PRIME DP - Unbound Medicine ER -