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

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.