title: Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo.
abstract: OBJECTIVE
  To study the pharmacodynamic properties of the subcutaneously injected long-acting insulin analog HOE901 (30 microg/ml zinc) in comparison with those of NPH insulin and placebo.
  
  
  METHODS
  In this single-center double-blind euglycemic glucose clamp study, 15 healthy male volunteers (aged 27 +/- 4 years, BMI 22.2 +/- 1.8 kg/m2) received single subcutaneous injections of 0.4 U/kg body wt of HOE901, NPH insulin, or placebo on 3 study days in a randomized order. The necessary glucose infusion rates (GIRs) to keep blood glucose concentrations constant at 5.0 mmol/l were determined over a 30-h period after administration.
  
  
  RESULTS
  The injection of HOE901 did not induce the pronounced peak in metabolic activity observed with NPH insulin (GIRmax 5.3 +/- 1.1 vs. 7.7 +/- 1.3 mg x kg(-1) x min(-1)) (P < 0.05); after an initial rise, metabolic activity was rather constant over the study period. This lack of peak was confirmed by a lower glucose consumption in the first 4 h after injection (area under the curve from 0 to 4 h [AUC(0-4 h)] 1.02 +/- 0.34 vs. 1.48 +/- 0.34 g/kg) (P < 0.001) with HOE901, as compared with NPH insulin. In this single-dose study, the metabolic effect measured over a period of 30 h was lower with HOE901 than with NPH insulin (AUC(0-30 h) 7.93 +/- 1.82 vs. 9.24 +/- 1.29 g/kg) (P < 0.05).
  
  
  CONCLUSIONS
  This study shows that the soluble long-acting insulin analog HOE901 induces a smoother metabolic effect than NPH insulin, from which a better substitution of basal insulin requirements may follow.
authors.affiliation: Department of Metabolic Diseases and Nutrition, the World Health Organization Collaborating Centre for Diabetes, Heinrich-Heine University, Düsseldorf, Germany. lutz.heinemann@profil-research.de
authors.forename: L
authors.initials: L
authors.lastname: Heinemann
authors.forename: R
authors.initials: R
authors.lastname: Linkeschova
authors.forename: K
authors.initials: K
authors.lastname: Rave
authors.forename: B
authors.initials: B
authors.lastname: Hompesch
authors.forename: M
authors.initials: M
authors.lastname: Sedlak
authors.forename: T
authors.initials: T
authors.lastname: Heise
mesh_terms: D000328:Adult; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015309:Glucose Clamp Technique; D006801:Humans; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D000069036:Insulin Glargine; D007336:Insulin, Isophane / Q000008:administration & dosage / Q000494:pharmacology*; D049528:Insulin, Long-Acting; D007700:Kinetics; D008297:Male; D010919:Placebos
chemical_list: D002096:C-Peptide; D007328:Insulin; D049528:Insulin, Long-Acting; D010919:Placebos; D000069036:Insulin Glargine; D007336:Insulin, Isophane