Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine. (August 2015)

• Record Type: Journal Article
• Authors: Heise, Tim; Hövelmann, Ulrike; Nosek, Leszek; Hermanski, Lidia; Bøttcher, Susanne G; Haahr, Hanne
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 11:Number 8(2015:Aug.)
• Page Start: 1193
• Page End: 1201
• Publication Date: 2015-08
• Subjects: Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1517/17425255.2015.1058779
• Languages: English
• ISSNs: 1742-5255

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Objectives: </italic> </bold>A medical need remains for a once-daily insulin with 24-h basal coverage in all patients. We characterize the steady-state (SS) pharmacokinetic/pharmacodynamic properties of insulin degludec (IDeg) versus insulin glargine (IGlar).</p> <p> <bold> <italic>Research design and methods: </italic> </bold>In this controlled, single-center study, 66 type 1 diabetes patients were randomized to two 8-day periods of once-daily IDeg or IGlar at 0.4, 0.6 or 0.8 U/kg. At SS, subjects underwent a 42-h euglycemic glucose clamp (5.5 mmol/l; 100 mg/dl). Glucose infusion rate (GIR), distribution of GIR and half-life were assessed.</p> <p> <bold> <italic>Results: </italic> </bold>Mean 24-h GIR profiles were flatter and more stable for all doses of IDeg versus IGlar. The evenly distributed glucose-lowering effect of IDeg was confirmed by the AUC<sub>GIR</sub> across one dosing interval, as each of the four 6-h intervals across one dosing interval contributed ∼ 25% of the AUC<sub>GIR, τ, SS</sub>. IGlar was most effective during the first 12 – 18 h after dosing. At SS, the half-life was 25.4 (IDeg) versus 12.1 h (IGlar). No safety concerns were identified for IDeg or IGlar.</p> <p> <bold> <italic>Conclusion: </italic> </bold>IDeg has a longer half-life (> 25 h) than IGlar. Exposure and glucose-lowering effects are more stable and evenly distributed across one dosing interval for IDeg versus IGlar (Clinical trials.gov identifier: NCT01114542).</p> </abstract>