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

Diabetes Obes Metab. 2016 Mar;18(3):274-80. doi: 10.1111/dom.12609. Epub 2016 Jan 11.

Abstract

Aims: 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.

Keywords: efficacy; insulin aspart; insulin degludec; insulin intensification; type 2 diabetes.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Glucose / analysis
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Glycated Hemoglobin / drug effects
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Insulin Aspart / administration & dosage*
  • Insulin Detemir / administration & dosage*
  • Insulin, Long-Acting / administration & dosage*
  • Male
  • Meals
  • Middle Aged

Substances

  • Blood Glucose
  • Drug Combinations
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin, Long-Acting
  • hemoglobin A1c protein, human
  • insulin degludec, insulin aspart drug combination
  • Insulin Detemir
  • Insulin Aspart