title: Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes.
abstract: OBJECTIVE
  Insulin degludec (IDeg) is a new-generation basal insulin with an ultra-long duration of action. We compared the pharmacodynamic (PD) variability of IDeg and insulin glargine (IGlar) under steady-state conditions.
  
  
  METHODS
  Day-to-day variability in glucose-lowering effect was investigated in 54 subjects with type 1 diabetes who underwent a 24-h euglycaemic glucose clamp on the 6th, 9th and 12th day of treatment with 0.4 U/kg of IDeg or IGlar once daily. Within-subject variability was estimated using a linear mixed model on log-transformed PD endpoints derived from the glucose infusion rate (GIR) profiles during the clamps.
  
  
  RESULTS
  For IDeg the day-to-day variability in glucose-lowering effect was four-times lower than for IGlar for total metabolic effect (AUC(GIR,0-24h,SS), CV 20% vs. 82%) and for the last 22 h [AUC(GIR,2-24h,SS) (not influenced by intravenous insulin during the clamp), CV 22% vs. 92%]. Furthermore, lower variability in the maximum effect was observed for IDeg vs. IGlar (GIR(max,SS), CV 18% vs. 60%). The lower within-subject variability of IDeg was consistent over time (CVs of 33% for AUC(GIR,0-2h,SS), 32% for AUC(GIR,10-12h,SS) and 33% for AUC(GIR,22-24h,SS)), whereas the variability of IGlar was higher and increased substantially 8 h post-dosing (CVs of 60% for AUC(GIR,0-2h,SS), 135% for AUC(GIR,10-12h,SS) and 115% for AUC(GIR,22-24h,SS)).
  
  
  CONCLUSIONS
  These results show that IDeg has a significantly more predictable glucose-lowering effect from day to day than IGlar.
authors.affiliation: Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany. tim.heise@profil.com
authors.forename: T
authors.initials: T
authors.lastname: Heise
authors.forename: L
authors.initials: L
authors.lastname: Hermanski
authors.forename: L
authors.initials: L
authors.lastname: Nosek
authors.forename: A
authors.initials: A
authors.lastname: Feldman
authors.forename: S
authors.initials: S
authors.lastname: Rasmussen
authors.forename: H
authors.initials: H
authors.lastname: Haahr
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000494:pharmacology*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine; C571886:insulin degludec