title: Comparison of pharmacokinetics and dynamics of the long-acting insulin analogs glargine and detemir at steady state in type 1 diabetes: a double-blind, randomized, crossover study.
abstract: OBJECTIVE
  To compare pharmacokinetics and pharmacodynamics of insulin analogs glargine and detemir, 24 subjects with type 1 diabetes (aged 38 +/- 10 years, BMI 22.4 +/- 1.6 kg/m2, and A1C 7.2 +/- 0.7%) were studied after a 2-week treatment with either glargine or detemir once daily (randomized, double-blind, crossover study).
  
  
  METHODS
  Plasma glucose was clamped at 100 mg/dl for 24 h after subcutaneous injection of 0.35 unit/kg. The primary end point was end of action (time at which plasma glucose was >150 mg/dl).
  
  
  RESULTS
  With glargine, plasma glucose remained at 103 +/- 3.6 mg/dl up to 24 h, and all subjects completed the study. Plasma glucose increased progressively after 16 h with detemir, and only eight subjects (33%) completed the study with plasma glucose <180 mg/dl. Glucose infusion rate (GIR) was similar with detemir and glargine for 12 h, after which it decreased more rapidly with detemir (P < 0.001). Estimated total insulin activity (GIR area under the curve [AUC](0-end of GIR)) was 1,412 +/- 662 and 915 +/- 225 mg/kg (glargine vs. detemir, P < 0.05), with median time of end of action at 24 and 17.5 h (glargine vs. detemir, P < 0.001). The antilipolytic action of detemir was lower than that of glargine (AUC free fatty acids(0-24 h) 11 +/- 1.7 vs. 8 +/- 2.8 mmol/l, respectively, P < 0.001).
  
  
  CONCLUSIONS
  Detemir has effects similar to those of glargine during the initial 12 h after administration, but effects are lower during 12-24 h.
authors.affiliation: Department of Internal Medicine, Section of Internal Medicine, Endocrinology and Metabolism, University of Perugia, Via E. Dal Pozzo, 06126 Perugia, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Porcellati
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossetti
authors.forename: Natalia Ricci
authors.initials: NR
authors.lastname: Busciantella
authors.forename: Stefania
authors.initials: S
authors.lastname: Marzotti
authors.forename: Paola
authors.initials: P
authors.lastname: Lucidi
authors.forename: Steven
authors.initials: S
authors.lastname: Luzio
authors.forename: David R
authors.initials: DR
authors.lastname: Owens
authors.forename: Geremia B
authors.initials: GB
authors.lastname: Bolli
authors.forename: Carmine G
authors.initials: CG
authors.lastname: Fanelli
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D007328:Insulin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069057:Insulin Detemir; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; D000069057:Insulin Detemir