title: Glucose-lowering effect of insulin degludec is independent of subcutaneous injection region.
abstract: OBJECTIVE
  Patients with diabetes mellitus inject insulin in different regions of the body. This study investigated the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a new-generation once-daily basal insulin with an ultra-long duration of action, after subcutaneous (SC) administration in different injection regions.
  
  
  METHODS
  In this study, 20 healthy subjects received single SC doses of IDeg (0.4 U/kg; separated by 13-21 days) in the thigh, abdomen and deltoid in a randomised, open-label, single-centre, single-dose, complete crossover trial. Each dose was followed by a 24-h euglycaemic clamp and 120-h pharmacokinetic blood sampling. The obtained pharmacokinetic/pharmacodynamic profiles were extrapolated to steady state by simulation using a pharmacokinetic/pharmacodynamic model.
  
  
  RESULTS
  Total IDeg exposure [area under the IDeg serum concentration-time curve 0-120 h after a single dose (AUCIDeg,0-120h,SD)] and maximum serum concentration [maximum IDeg serum concentration after a single dose (C max,IDeg,SD)] were higher (6-7 and 23-27 %, respectively) following a single SC dose in the deltoid or abdomen, compared with the thigh, as also observed with other insulin preparations. No statistical difference was observed in these measures between deltoid and abdominal administration. No pronounced differences were observed in the glucose-lowering effect of IDeg [area under the glucose infusion rate (GIR) curve 0-24 h after a single dose (AUCGIR,0-24h,SD) and maximum GIR after a single dose (GIRmax,SD)] when injected in the thigh, abdomen or deltoid (AUCGIR,0-24h,SD 2,572, 2,833 and 2,960 mg/kg, respectively). Simulated mean steady-state pharmacokinetic and pharmacodynamic profiles supported a flat and stable IDeg exposure and effect regardless of injection region, with comparable total glucose-lowering effects [area under the GIR curve at steady state (AUCGIR,τ,SS)] between the thigh, abdomen and deltoid.
  
  
  CONCLUSIONS
  These findings support administering IDeg SC in the thigh, upper arm or abdominal wall without affecting IDeg absorption or effect at steady state.
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Hellersbergstraße 9, 41460, Neuss, Germany, leszek.nosek@profil.com.
authors.forename: Leszek
authors.initials: L
authors.lastname: Nosek
authors.forename: Hans-Veit
authors.initials: HV
authors.lastname: Coester
authors.forename: Carsten
authors.initials: C
authors.lastname: Roepstorff
authors.forename: Henrik F
authors.initials: HF
authors.lastname: Thomsen
authors.forename: Niels R
authors.initials: NR
authors.lastname: Kristensen
authors.forename: Hanne
authors.initials: H
authors.lastname: Haahr
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects*; D018592:Cross-Over Studies; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous / Q000379:methods; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C571886:insulin degludec