title: Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes.
abstract: The aim of this randomized double-blind study was to compare the within-subject variability of the glucose-lowering effect of a novel insulin analog, insulin detemir, with that of insulin glargine and NPH insulin in people with type 1 diabetes. Fifty-four subjects (32 males and 22 females, age 38 +/- 10 years [mean +/- SD], BMI 24 +/- 2 kg/m(2), HbA(1c) 7.5 +/- 1.2%, diabetes duration 18 +/- 9 years) participated in this parallel group comparison. Each subject received four single subcutaneous doses of 0.4 units/kg of either insulin detemir (n = 18), insulin glargine (n = 16), or human NPH insulin (n = 17) under euglycemic glucose clamp conditions (target blood glucose concentration 5.5 mmol/l) on four identical study days. The pharmacodynamic (glucose infusion rates [GIRs]) and pharmacokinetic (serum concentrations of insulin detemir, human insulin, and insulin glargine) properties of the basal insulin preparations were recorded for 24 h postdosing. Insulin detemir was associated with significantly less within-subject variability than both NPH insulin and insulin glargine, as assessed by the coefficient of variation (CV) for the pharmacodynamic end points studied [GIR-AUC((0-12 h)) 27% (detemir) vs. 59% (NPH) vs. 46% (glargine); GIR-AUC((0-24 h)) 27 vs. 68 vs. 48%; GIR(max) 23 vs. 46 vs. 36%; P < 0.001 for all comparisons]. Insulin detemir also provided less within-subject variability in the pharmacokinetic end points: maximal concentration (C(max)) 18 vs. 24 vs. 34%; INS-AUC((0- infinity )) 14 vs. 28 vs. 33%. The results suggest that insulin detemir has a significantly more predictable glucose-lowering effect than both NPH insulin and insulin glargine.
authors.affiliation: Profil Institut für Stoffwechselforschung, Hellersbergstr. 9, D-41460 Neuss, Germany. tim.heise@profil-research.de
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
authors.forename: Leszek
authors.initials: L
authors.lastname: Nosek
authors.forename: Birgitte Biilmann
authors.initials: BB
authors.lastname: Rønn
authors.forename: Lars
authors.initials: L
authors.lastname: Endahl
authors.forename: Lutz
authors.initials: L
authors.lastname: Heinemann
authors.forename: Christoph
authors.initials: C
authors.lastname: Kapitza
authors.forename: Eberhard
authors.initials: E
authors.lastname: Draeger
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use*; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D002352:Carrier Proteins; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; D000069057:Insulin Detemir; D007336:Insulin, Isophane; D005947:Glucose