title: Insulin degludec: Lower day-to-day and within-day variability in pharmacodynamic response compared with insulin glargine 300 U/mL in type 1 diabetes.
abstract: To compare day-to-day and within-day variability in glucose-lowering effect between insulin degludec (IDeg) and insulin glargine 300 U/mL (IGlar-U300) in type 1 diabetes.
  
  
  
  In this double-blind, crossover study, patients were randomly assigned to 0.4 U/kg of IDeg or IGlar-U300 once daily for two treatment periods lasting 12 days each. Pharmacodynamic variables were assessed at steady-state from the glucose infusion rate profiles of three 24-hour euglycaemic glucose clamps (days 6, 9 and 12) during each treatment period.
  
  
  
  Overall, 57 patients completed both treatment periods (342 clamps). The potency of IGlar-U300 was 30% lower than IDeg (estimated ratio 0.70, 95% confidence interval [CI] 0.61; 0.80; P  < .0001). The distribution of glucose-lowering effect was stable across 6-hour intervals (24%-26%) for IDeg, while IGlar-U300 had greater effects in the first (35%) and last (28%) intervals compared with 6 to 12 hours (20%) and 12 to 18 hours (17%). Within-day variability (relative fluctuation) was 37% lower with IDeg than with IGlar-U300 (estimated ratio IDeg/IGlar-U300: 0.63, 95% CI 0.54; 0.73; P  < .0001). The day-to-day variability in glucose-lowering effect with IDeg was approximately 4 times lower than IGlar-U300 (variance ratio IGlar-U300/IDeg: 3.70, 95% CI 2.42; 5.67; P  < .0001). The day-to-day variability in glucose-lowering effect assessed in 2-hour intervals was consistently low with IDeg over 24 hours, but steadily increased with IGlar-U300 to a maximum at 10 to 12 hours and 12 to 14 hours after dosing (variance ratios 12.4 and 11.4, respectively).
  
  
  
  IDeg has lower day-to-day and within-day variability than IGlar-U300 and a more stable glucose-lowering effect, which might facilitate titration and enable tighter glycaemic control with a reduced risk of hypoglycaemia.
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Tim
authors.identifier: 0000-0002-8346-2037
authors.initials: T
authors.lastname: Heise
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Nørskov
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Leszek
authors.initials: L
authors.lastname: Nosek
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Kadriye
authors.initials: K
authors.lastname: Kaplan
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Famulla
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Hanne L
authors.initials: HL
authors.lastname: Haahr
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069036:Insulin Glargine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007333:Insulin Resistance; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human; C571886:insulin degludec
keywords: insulin analogues; insulin therapy; pharmacodynamics; type 1 diabetes