title: A direct comparison of the pharmacodynamic properties of insulin detemir and neutral protamine lispro insulin in patients with type 1 diabetes.
abstract: OBJECTIVE
  To compare the pharmacodynamic properties of insulin detemir (detemir) and neutral protamine lispro (NPL) insulin using a euglycaemic glucose clamp.
  
  
  METHODS
  In a double-blind, crossover study, 30 patients with C-peptide negative type 1 diabetes were randomly assigned to a single dose (0.4 U/kg) of detemir and NPL. Plasma glucose (PG) was normalized with a variable insulin infusion and then decreased stepwise, followed by a euglycaemic clamp at 5.5 mmol/l over 32 h. Duration of action was defined as time from dosing until PG exceeded 8.3 mmol/l for at least 30 min.
  
  
  RESULTS
  Duration of action was similar for detemir [23.0 (range 2.25-32) h] and NPL [22.0 (9.5-32) h], p = 0.55. Using glucose infusion rate (GIR) parameters, detemir showed a flatter pharmacodynamic profile versus NPL: area under the curve, AUC(GIR)             ((0-32))  = 1326 vs. 1841 mg/kg, p < 0.01 (detemir vs. NPL, respectively); AUC(GIR)             ((0-12))  = 784 vs. 1392 mg/kg, p < 0.05; AUC(GIR)             ((12-32))  = 455 vs. 274 mg/kg, p = 0.051; GIR(late) (12-32)/GIR(early) (0-12) ratio = 0.33 vs. 0.04, p < 0.001. Detemir also showed a lower and later peak of action than NPL [GIR(max)  2.0 vs. 3.2 mg/kg/min, p < 0.01; T(max)  9.1 (95% confidence interval: 3.0-14.7) vs. 7.0 h (1.8-15.2)].
  
  
  CONCLUSIONS
  Detemir and NPL had similar duration of action of approximately 24 h in patients with type 1 diabetes. Compared with NPL, detemir had a flatter profile with a more even distribution of metabolic effect over 24 h.
authors.affiliation: Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors.forename: S
authors.initials: S
authors.lastname: Korsatko
authors.forename: K
authors.initials: K
authors.lastname: Glettler
authors.forename: K J
authors.initials: KJ
authors.lastname: Olsen
authors.forename: A
authors.initials: A
authors.lastname: Wutte
authors.forename: G
authors.initials: G
authors.lastname: Bock
authors.forename: G
authors.initials: G
authors.lastname: Koehler
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: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015992:Body Mass Index; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011479:Protamines / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D011479:Protamines; C110077:neutral protamine lispro insulin; D000069057:Insulin Detemir