title: Treatment intensification with an insulin degludec (IDeg)/insulin aspart (IAsp) co-formulation twice daily compared with basal IDeg and prandial IAsp in type 2 diabetes: a randomized, controlled phase III trial.
abstract: OBJECTIVE
  To evaluate the efficacy and safety of two insulin intensification strategies for patients with type 2 diabetes previously treated with basal insulin--insulin degludec (IDeg) and insulin aspart (IAsp)--administered as a co-formulation (IDegAsp) or as a basal-bolus regimen (IDeg and IAsp in separate injections).
  
  
  METHODS
  This 26-week, open-label, treat-to-target, phase IIIb, non-inferiority trial randomized patients (1 : 1) to IDegAsp twice daily with main meals (n = 138; IDegAsp group) or IDeg once daily and IAsp 2-4 times daily (n = 136; IDeg+IAsp group).
  
  
  RESULTS
  After 26 weeks, the mean glycated haemoglobin (HbA1c) level was 7.0% (53 mmol/mol) for the IDegAsp group and 6.8% (51 mmol/mol) for the IDeg+IAsp group (Δ%HbA1c from baseline -1.31 and -1.50%, respectively). The non-inferiority of IDegAsp versus IDeg+IAsp was not confirmed for mean change in HbA1c [estimated treatment difference (ETD) 0.18, 95% confidence interval (CI) -0.04, 0.41; p = non-significant]. No significant differences were observed in the proportion of patients achieving HbA1c <7.0% (56.5 and 59.6%, respectively). IDegAsp treatment resulted in a significantly lower total daily insulin dose, a smaller change in body weight, numerically lower rates of confirmed hypoglycaemia (self-reported plasma glucose <3.1 mmol/l; rate ratio 0.81; p = non-significant), and nocturnal confirmed hypoglycaemic episodes (rate ratio 0.80; p = non-significant) versus IDeg+IAsp. Patient-reported outcome scores for social functioning were significantly higher for IDegAsp versus IDeg+IAsp (ETD 2.2; 95% CI 0.3, 4.1; p < 0.05).
  
  
  CONCLUSIONS
  Both intensification strategies effectively improved glycaemic control. Although non-inferiority was not confirmed, there were no significant differences between the groups that could affect clinical utility.
authors.affiliation: Endocrine and Metabolic Consultants, Rockville, MD, USA.
authors.forename: H W
authors.initials: HW
authors.lastname: Rodbard
authors.affiliation: Department of Endocrinology, l'Institut du Thorax, Nantes University Hospital, Nantes, France.
authors.forename: B
authors.initials: B
authors.lastname: Cariou
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Metabolism, Medical University of Graz, Graz, Austria.
authors.forename: T R
authors.initials: TR
authors.lastname: Pieber
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: L A
authors.initials: LA
authors.lastname: Endahl
authors.affiliation: Novo Nordisk A/S, Søborg, Denmark.
authors.forename: J
authors.initials: J
authors.lastname: Zacho
authors.affiliation: Department of Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: J G
authors.initials: JG
authors.lastname: Cooper
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D061267:Insulin Aspart / Q000008:administration & dosage*; D000069057:Insulin Detemir / Q000008:administration & dosage*; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D008297:Male; D062407:Meals; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D061267:Insulin Aspart; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human; C578220:insulin degludec, insulin aspart drug combination
keywords: efficacy; insulin aspart; insulin degludec; insulin intensification; type 2 diabetes