title: Proportional dose-response relationship and lower within-patient variability of insulin detemir and NPH insulin in subjects with type 1 diabetes mellitus.
abstract: OBJECTIVE
  This study was conducted to evaluate the dose ratio of insulin detemir and neutral protamine Hagedorn (NPH) insulin over a range of therapeutically relevant subcutaneous doses.
  
  
  METHODS
  The study was a randomized, double-blind, crossover 24-h-iso-glycemic clamp trial in 12 C-peptide-negative type 1 diabetic patients. Each subject received, by an incomplete block design selection, two of three possible doses of insulin detemir (0.15, 0.3, 0.6 U/kg) and NPH insulin (0.15, 0.3, 0.6 IU/kg), respectively. A detailed assessment of endogenous glucose production (EGP) and glucose uptake was performed, by use of stable isotopic labeled glucose tracer (D-[6,6- (2)H (2)] glucose).
  
  
  RESULTS
  Dose proportionality was observed within the tested dose range. Regarding unit dose ratio, 0.68 U insulin detemir equals 1 IU NPH insulin (95% CI [0.35; 1.30]). There was no statistically significant difference in effect on the area under the curve (AUC) of glucose infusion rate (GIR) (AUC (GIR)) and the maximal GIR (GIR (max)) values, when comparing U (insulin detemir) to IU (NPH insulin). The pharmacodynamic within-subject profile was lower with insulin detemir in regard to AUC (GIR 0-24 h), GIR (max) and duration of action ( P<0.05). There was a tendency for a greater reduction of EGP with insulin detemir than with NPH insulin in regard to the area over the curve (AOC) of EGP in 24 hours (AOC (EGP 0-24 h)) ( P=0.07) and minimal EPG (EGP (min)) ( P=0.02).
  
  
  CONCLUSIONS
  These data show that insulin detemir is dose-proportional to NPH insulin in type 1 diabetic patients at clinically relevant doses. The data indicate that insulin detemir has a lower degree of within-subject variability.
authors.affiliation: Department of Internal Medicine, Diabetes and Metabolism, Medical University of Graz, Austria. andrea.wutte@healthsite.at
authors.forename: A
authors.initials: A
authors.lastname: Wutte
authors.forename: J
authors.initials: J
authors.lastname: Plank
authors.forename: M
authors.initials: M
authors.lastname: Bodenlenz
authors.forename: C
authors.initials: C
authors.lastname: Magnes
authors.forename: W
authors.initials: W
authors.lastname: Regittnig
authors.forename: F
authors.initials: F
authors.lastname: Sinner
authors.forename: B
authors.initials: B
authors.lastname: Rønn
authors.forename: M
authors.initials: M
authors.lastname: Zdravkovic
authors.forename: T R
authors.initials: TR
authors.lastname: Pieber
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis / Q000378:metabolism; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069057:Insulin Detemir; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007328:Insulin; D049528:Insulin, Long-Acting; D000069057:Insulin Detemir; D007336:Insulin, Isophane; D005947:Glucose