AIM: The metabolic efficacy of adding prandial insulin in a stepwise manner to a straightforward basal-bolus regimen was compared in patients with type 2 diabetes mellitus (T2DM), suboptimally controlled by oral antidiabetic drugs (OADs) and once-daily basal insulin. METHODS: In this international randomized, parallel-group, non-inferiority study, 811 patients with poorly controlled type 2 diabetes using basal insulin were switched toinsulin glargine (GLAR) for 6 months while continuing OADs. Patients with HbA(1c) > 7% and FPG < 120 mg/dL (n=476) were then randomized to either group 1, GLAR+metformin (MET)+3×insulin glulisine (GLU), group 2, GLAR+MET+1-3×GLU, or group 3, GLAR+MET+insulin secretagogue (IS)+1-3×GLU, for 12 months. Objectives were to show the non-inferiority of efficacy of group 2 vs group 1 and vs group 3. Non-inferiority of group 2 vs group 1 was concluded if the upper limit of the 95% confidence interval (CI) for the HbA(1c) difference was ≤ to 0.4%. RESULTS: The adjusted HbA(1c) difference of group 2 vs 1 for the per-protocol population crossed the non-inferiority margin (0.228, 95% CI: -0.018-0.473). There was significantly less weight gain in group 2 compared with group 1, but adverse events were otherwise similar between the two groups. In patients with HbA(1c) < 8% at baseline, non-inferiority was achieved in group 2 vs group 1. CONCLUSION: Although non-inferiority was not achieved, stepwise intensification of GLU added to GLAR showed efficacy close to that of the basal-bolus approach and with significantly less weight gain.
RCT Entities:
AIM: The metabolic efficacy of adding prandial insulin in a stepwise manner to a straightforward basal-bolus regimen was compared in patients with type 2 diabetes mellitus (T2DM), suboptimally controlled by oral antidiabetic drugs (OADs) and once-daily basal insulin. METHODS: In this international randomized, parallel-group, non-inferiority study, 811 patients with poorly controlled type 2 diabetes using basal insulin were switched to insulinglargine (GLAR) for 6 months while continuing OADs. Patients with HbA(1c) > 7% and FPG < 120 mg/dL (n=476) were then randomized to either group 1, GLAR+metformin (MET)+3×insulinglulisine (GLU), group 2, GLAR+MET+1-3×GLU, or group 3, GLAR+MET+insulin secretagogue (IS)+1-3×GLU, for 12 months. Objectives were to show the non-inferiority of efficacy of group 2 vs group 1 and vs group 3. Non-inferiority of group 2 vs group 1 was concluded if the upper limit of the 95% confidence interval (CI) for the HbA(1c) difference was ≤ to 0.4%. RESULTS: The adjusted HbA(1c) difference of group 2 vs 1 for the per-protocol population crossed the non-inferiority margin (0.228, 95% CI: -0.018-0.473). There was significantly less weight gain in group 2 compared with group 1, but adverse events were otherwise similar between the two groups. In patients with HbA(1c) < 8% at baseline, non-inferiority was achieved in group 2 vs group 1. CONCLUSION: Although non-inferiority was not achieved, stepwise intensification of GLU added to GLAR showed efficacy close to that of the basal-bolus approach and with significantly less weight gain.