Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine

Abstract

Objectives: 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).

Research design and methods: 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.

Results: 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_GIR across one dosing interval, as each of the four 6-h intervals across one dosing interval contributed ∼ 25% of the AUC_GIR,τ,SS. 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.

Conclusion: 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).

Keywords:

• euglycemic glucose clamp
• insulin degludec
• insulin glargine
• pharmacodynamics
• pharmacokinetics
• type 1 diabetes

Declaration of interest

This study was funded by Novo Nordisk A/S. Physician time was paid for at normal rates. Data processing and statistical analysis were performed by Novo Nordisk A/S, who also coordinated the study. T Heise is a shareholder of Profil, Neuss, Germany. Within the past year, this institution received research funds from Adocia, Becton Dickinson, Biocon, Boehringer Ingelheim, Bristol-Myers Squibb, Dance Pharmaceuticals, Evolva, Hoffmann La-Roche, Johnson & Johnson, Eli Lilly, Marvel, Novartis, Novo Nordisk, Sanofi and Servier. In addition, T Heise received speaker honoraria from Eli Lilly and Novo Nordisk, received travel grants from Novo Nordisk and is a member of advisory panels for Novo Nordisk. SG Bøttcher is an employee of Novo Nordisk A/S. H Haahr is an employee and shareholder of Novo Nordisk A/S. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical writing support was provided by Edward Kitchen and Dr Nason Ma’ani, apothecom scopemedical Ltd, London, UK, and by Carsten Roepstorff, Larix A/S, Copenhagen, Denmark, funded by Novo Nordisk.

Notes