title: Comparison of the pharmacokinetic and pharmacodynamic profiles of insulin degludec and insulin glargine.
abstract: OBJECTIVE
  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).
  
  
  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.
  
  
  CONCLUSIONS
  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).
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH , Hellersbergstr. 9, D-41460 Neuss , Germany + 49 2131 4018 411 ; Tim.Heise@profil.com.
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hövelmann
authors.forename: Leszek
authors.initials: L
authors.lastname: Nosek
authors.forename: Lidia
authors.initials: L
authors.lastname: Hermanski
authors.forename: Susanne G
authors.initials: SG
authors.lastname: Bøttcher
authors.forename: Hanne
authors.initials: H
authors.lastname: Haahr
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D000069036:Insulin Glargine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; C571886:insulin degludec
keywords: euglycemic glucose clamp; insulin degludec; insulin glargine; pharmacodynamics; pharmacokinetics; type 1 diabetes