Mader, J.K., Jensen, L., Ingwersen, S.H. et al. (3 more authors) (2016) Pharmacokinetic Properties of Liraglutide as Adjunct to Insulin in Subjects with Type 1 Diabetes Mellitus. Clinical Pharmacokinetics. ISSN 0312-5963
Abstract
BACKGROUND: The pharmacokinetic properties of liraglutide, a glucagon-like peptide-1 receptor agonist approved for the treatment of type 2 diabetes mellitus (T2D), have been established in healthy individuals and subjects with T2D. Liraglutide has been under investigation as adjunct treatment to insulin in type 1 diabetes mellitus (T1D). This single-center, double-blind, placebo-controlled, crossover, clinical pharmacology trial is the first to analyze the pharmacokinetic properties of liraglutide as add-on to insulin in T1D. METHODS: Subjects (18-64 years; body mass index 20.0-28.0 kg/m(2); glycated hemoglobin ≤9.5 %) were randomized 1:1:1 to 0.6, 1.2, or 1.8 mg liraglutide/placebo. Each group underwent two 4-week treatment periods (liraglutide then placebo or placebo then liraglutide) separated by a 2- to 3-week washout. Both trial drugs were administered subcutaneously, once daily, as adjunct to insulin. A stepwise hypoglycemic clamp was performed at the end of each treatment period (data reported previously). Pharmacokinetic endpoints were derived from liraglutide concentration-time curves after the final dose and exposure was compared with data from previous trials in healthy volunteers and subjects with T2D. RESULTS: The pharmacokinetic properties of liraglutide in T1D were comparable with those observed in healthy volunteers and subjects with T2D. Area under the steady-state concentration-time curve (AUC) and maximum plasma concentration data were consistent with dose proportionality of liraglutide. Comparison of dose-normalized liraglutide AUC suggested that exposure in T1D, when administered with insulin, is comparable with that observed in T2D. CONCLUSIONS: Liraglutide, administered as adjunct to insulin in subjects with T1D, shows comparable pharmacokinetics to those in subjects with T2D. ClinicalTrials.gov Identifier: NCT01536665.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 21 Sep 2016 09:07 |
Last Modified: | 21 Sep 2016 09:07 |
Published Version: | http://dx.doi.org/10.1007/s40262-016-0413-4 |
Status: | Published |
Publisher: | Springer Verlag |
Refereed: | Yes |
Identification Number: | 10.1007/s40262-016-0413-4 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:104943 |