title: Insulin degludec/insulin aspart administered once daily at any meal, with insulin aspart at other meals versus a standard basal-bolus regimen in patients with type 1 diabetes: a 26-week, phase 3, randomized, open-label, treat-to-target trial.
abstract: OBJECTIVE
  To evaluate efficacy and tolerability of a co-formulation of insulin degludec and insulin aspart (IDegAsp) with insulin aspart (IAsp) at other meals compared with basal-bolus therapy using insulin detemir (IDet) and IAsp.
  
  
  METHODS
  Adults (n = 548) with type 1 diabetes (A1C 7.0-10.0%; BMI ≤35.0 kg/m(2)) were randomized 2:1 in a 26-week, multinational, parallel-group, treat-to-target trial to IDegAsp or IDet. IDegAsp was given with a meal, and IDet was given in the evening, with a second (breakfast) dose added if needed.
  
  
  RESULTS
  Non-inferiority for IDegAsp versus IDet was confirmed; A1C improved by 0.75% with IDegAsp and 0.70% with IDet to 7.6% in both groups (estimated treatment difference IDegAsp - IDet: -0.05% [95% CI -0.18 to 0.08]). There was no statistically significant difference between IDegAsp and IDet in the rates of severe hypoglycemia (0.33 and 0.42 episodes/patient-year, respectively) or overall confirmed (plasma glucose <3.1 mmol/L) hypoglycemia (39.17 and 44.34 episodes/patient-year, respectively). Nocturnal confirmed hypoglycemia rate was 37% lower with IDegAsp than IDet (3.71 vs. 5.72 episodes/patient-year, P < 0.05). Weight gain was 2.3 and 1.3 kg with IDegAsp and IDet, respectively (P < 0.05). Total insulin dose was 13% lower in the IDegAsp group (P < 0.0001). No treatment differences were detected in Health-Related Quality of Life, laboratory measurements, physical examination, vital signs, electrocardiograms, fundoscopy, or adverse events.
  
  
  CONCLUSIONS
  IDegAsp in basal-bolus therapy with IAsp at additional mealtimes improves overall glycemic control and was non-inferior to IDet, with a reduced risk of nocturnal hypoglycemia and fewer injections in comparison with IDet + IAsp basal-bolus therapy.
authors.affiliation: University of Washington Medical Center-Roosevelt, Seattle, WA, USA. ihirsch@u.washington.edu
authors.forename: Irl B
authors.initials: IB
authors.lastname: Hirsch
authors.forename: Bruce
authors.initials: B
authors.lastname: Bode
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Courreges
authors.forename: Patrik
authors.initials: P
authors.lastname: Dykiel
authors.forename: Edward
authors.initials: E
authors.lastname: Franek
authors.forename: Kjeld
authors.initials: K
authors.lastname: Hermansen
authors.forename: Allen
authors.initials: A
authors.lastname: King
authors.forename: Henriette
authors.initials: H
authors.lastname: Mersebach
authors.forename: Melanie
authors.initials: M
authors.lastname: Davies
mesh_terms: D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use*; D061267:Insulin Aspart / Q000008:administration & dosage* / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000008:administration & dosage* / Q000627:therapeutic use*; D062407:Meals
chemical_list: D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C571886:insulin degludec; D061267:Insulin Aspart