Comparison of insulin lispro protamine suspension versus insulin glargine once daily added to oral antihyperglycaemic medications and exenatide in type 2 diabetes: A prospective randomized open-label trial

摘要

Aims: To compare efficacy and safety of two, once-daily basal insulin formulations [insulin lispro protamine suspension (ILPS) vs. insulin glargine (glargine)] added to oral antihyperglycaemic medications (OAMs) and exenatide BID in suboptimally controlled type 2 diabetes (T2D) patients. Methods: This 24-week, open-label, multicentre trial randomized patients to bedtime ILPS (n=171) or glargine (n=168). Non-inferiority of ILPS versus glargine was assessed by comparing the upper limit of 95% confidence intervals (CIs) for change in haemoglobin A1c (HbA1c) from baseline to week 24 (adjusted for baseline HbA1c) with non-inferiority margin 0.4%. Results: Non-inferiority of ILPS versus glargine was demonstrated: least-squares mean between-treatment difference (ILPS minus glargine) (95% CI) was 0.22% (0.06, 0.38). Mean HbA1c reduction was less for ILPS- versus glargine-treated patients (-1.16±0.84 vs. -1.40±0.97%, p=0.008). Endpoint HbA1c<7.0% was achieved by 53.7% (ILPS) and 61.7% (glargine) (p=NS). Overall hypoglycaemia rates (p=NS) and severe hypoglycaemia incidence (p=NS) were similar. Nocturnal hypoglycaemia rate was higher in patients treated with ILPS versus glargine (p=0.004). Weight gain was similar between groups (ILPS: 0.27±3.38kg; glargine: 0.66±3.93kg, p=NS). Endpoint total insulin doses were lower in patients treated with ILPS versus glargine (0.30±0.17 vs. 0.37±0.17IU/kg/day, p<0.001). Conclusions: ILPS was non-inferior to glargine for HbA1c change over 24weeks, but was associated with less HbA1c reduction and more nocturnal hypoglycaemia. Treat-to-target basal insulin therapy improves glycaemic control and is associated with minimal weight gain when added to OAMs and exenatide BID for suboptimally controlled T2D.