title: Pharmacodynamics of the long-acting insulin analogues detemir and glargine following single-doses and under steady-state conditions in patients with type 1 diabetes.
abstract: OBJECTIVE
  The pharmacodynamic characteristics of the basal insulin analogues insulin detemir (IDet) and insulin glargine (IGlar) have been examined extensively via euglycaemic clamp studies. However, differences in clamp methodology and in the analysis of clamp data between trials have led to confusion over the duration of action of these two insulins. The aim of this study was to address these ambiguities in the literature by assessing the pharmacodynamic properties of IDet and IGlar over 30 h under single-dose and steady-state conditions using the definitions and procedures previously standardized by Heise and Pieber in 2007.
  
  
  METHODS
  This was a single-centre, randomized, double-blind, glucose clamp trial involving 36 patients with type 1 diabetes.
  
  
  RESULTS
  The mean duration of action of IDet was 25.9 h, compared with 19.8 h for IGlar after a single-dose (NS), and 23.3 h (IDet) versus 27.1 h (IGlar) at steady-state (p < 0.0001). IDet had a significantly higher area under the curve glucose infusion rate (AUCGIR ) than IGlar over 0-12 h after a single-dose (p = 0.0018). The steady-state AUCGIR for IDet was numerically higher than IGlar over 0-12 h (728 vs. 592 mg/kg, respectively; p = NS), but significantly lower than IGlar at 12-30 h (p = 0.0003).
  
  
  CONCLUSIONS
  The duration of action of IDet is 23 h (range: 4.0-30.0), while that of IGlar is 27 h (range: 10.5-29.0) (95% CI: -8.1, 0.6). This suggests both insulins can be used for once-daily dosing, but individual needs must be considered.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Koehler
authors.forename: G
authors.initials: G
authors.lastname: Treiber
authors.forename: A
authors.initials: A
authors.lastname: Wutte
authors.forename: S
authors.initials: S
authors.lastname: Korsatko
authors.forename: J K
authors.initials: JK
authors.lastname: Mader
authors.forename: B
authors.initials: B
authors.lastname: Semlitsch
authors.forename: T R
authors.initials: TR
authors.lastname: Pieber
mesh_terms: D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; D000069057:Insulin Detemir
keywords: diabetes mellitus; insulin analogues; pharmacology; type 1 diabetes