Prandial-basal insulin regimens plus oral antihyperglycaemic agents to improve mealtime glycaemia: initiate and progressively advance insulin therapy in type 2 diabetes.

Aims: To compare two progressive approaches [once-daily insulin glargine plus ≤3 mealtime lispro (G+L) vs. insulin lispro mix 50/50 (LM50/50) progression once up to thrice daily (premix progression, PP)] of beginning and advancing insulin in patients with type 2 diabetes (T2D) and inadequate glycaemic control on oral therapy, with the aim of showing non-inferiority of PP to G+L. Methods: Patients were randomized to PP (n = 242) or G+L (n = 242) in a 36-week, multinational, open-label trial. Dinnertime insulin LM 50/50 could be replaced with insulin lispro mix 75/25 if needed for fasting glycaemic control. Results: Baseline haemoglobin A1c (HbA1c) were 9.5% (PP) and 9.3% (G+L); p = 0.095. Change in A1C (baseline to endpoint) was −1.76% (PP) and −1.93% (G+L) (p = 0.097) [between-group difference of 0.17 (95% confidence interval: −0.03, 0.37)]. Non-inferiority of PP to G+L was not shown based on the prespecified non-inferiority margin of 0.3%. A1C was lower with G+L at weeks 12 (7.8 vs. 7.9%; p = 0.042), 24 (7.4 vs. 7.6%; p = 0.046), but not at week 36 (7.5 vs. 7.6%; p = 0.405). There were no significant differences in percentages of patients achieving A1C ≤7%, overall hypoglycaemia incidence and rate or weight change. Total daily insulin dosages at endpoint were higher with PP vs. G+L (0.57 vs. 0.51 U/kg; p = 0.017), likely due to more injections (1.98 vs. 1.79; p = 0.011). Conclusions: Both treatments progressively improved glycaemic control in patients with T2D on oral therapy, although non-inferiority of PP to G+L was not shown. Higher insulin doses were observed with PP with no between-treatment differences in overall hypoglycaemia or weight gain.