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Expert Opin Drug Metab Toxicol. 2015;11(8):1193-201. doi: 10.1517/17425255.2015.1058779. Epub 2015 Jun 18.

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

Author information

1
Profil Institut für Stoffwechselforschung GmbH , Hellersbergstr. 9, D-41460 Neuss , Germany + 49 2131 4018 411 ; Tim.Heise@profil.com.

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 AUCGIR across one dosing interval, as each of the four 6-h intervals across one dosing interval contributed ∼ 25% of the AUCGIR,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

PMID:
26086190
DOI:
10.1517/17425255.2015.1058779
[Indexed for MEDLINE]

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