Efficacy and safety of insulin glulisine in Japanese patients with type 1 diabetes mellitus

Abstract

The rapid-acting insulin analogue insulin glulisine (glulisine) was compared with insulin lispro (lispro) for efficacy and safety in Japanese patients with type 1 diabetes mellitus (T1DM), using insulin glargine (glargine) as basal insulin. This was an open, randomized, parallel-group, comparative non-inferiority study. The primary efficacy measure was change in adjusted mean haemoglobin A1c (HbA1c) from baseline to endpoint. Safety and treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) were also assessed. Patients were treated for 28 weeks with either glulisine or lispro administered 0-15 min before a meal. Doses were titrated to obtain 2-h postprandial plasma glucose (2h-PPG) of 7.11-9.55 mmol/l (128-172 mg/dl). All patients were concomitantly treated with glargine at bedtime, titrated to obtain a fasting (prebreakfast) plasma glucose level of 5.27-7.11 mmol/l (95-128 mg/dl). Baseline mean HbA1c values were similar for the glulisine (n = 132) and lispro (n = 135) groups (7.44 and 7.50% respectively). From baseline to endpoint, adjusted mean HbA1c increased by 0.10% in the glulisine group and by 0.04% in the lispro group. Non-inferiority of glulisine compared with lispro was shown. There were no significant differences between glulisine and lispro in adjusted mean 2h-PPG [glulisine, 9.06 mmol/l (163 mg/dl) vs. lispro, 8.13 mmol/l (146 mg/dl); p = 0.065] and change in adjusted mean daily rapid-acting insulin dose (glulisine, 0.26 U vs. lispro, 0.26 U; p = 0.994) at study endpoint. There was a significant difference for change in adjusted mean daily basal insulin dose from baseline to study endpoint (glulisine, -0.54 U vs. lispro, 0.26 U; p = 0.013). The most common serious adverse events were hypoglycaemia-related events (hypoglycaemia, hypoglycaemic seizure and hypoglycaemic coma) with no difference observed between the two groups [glulisine, 6.8% (9/132) vs. lispro, 4.4% (6/135); p = 0.437]. No noteworthy differences were observed for change in insulin antibodies from baseline to endpoint. Assessment of treatment satisfaction score and perceived frequency of hyperglycaemia and hypoglycaemia by DTSQ showed no changes from baseline in either group. Glulisine was as effective as lispro with respect to change in HbA1c and was well tolerated when used in combination with glargine in Japanese patients with T1DM.