Effects of insulin glulisine as mono- or add-on therapy in patients with type 2 diabetes mellitus

Aim: To evaluate the safety and efficacy of insulin glulisine (glulisine) with and without oral antidiabetic drugs (OAD; sulphonylurea or sulphonylurea + biguanide) relative to that of OAD alone in Japanese and Korean patients with inadequately controlled type 2 diabetes mellitus (T2DM). Methods: In an open, randomized, parallel-group, comparative, controlled trial, 387 patients were randomized and treated with glulisine + OAD (n = 130), glulisine monotherapy (n = 127) or OAD only (n = 130) for 16 weeks. Glulisine was self-injected subcutaneously three times daily (0-15 minutes before meals) at a starting dose of ≥0.2 U/kg/day. Patients titrated the glulisine dose to achieve a 2-h postprandial plasma glucose (2h-PPG) level of 7.1-9.5 mmol/l (128-172 mg/dl) by administering at least one additional unit at each appropriate meal time if the 2h-PPG level was > 9.5 and < 11.1 mmol/l (> 172 and < 200 mg/dl) and by administering at least two additional units if the 2h-PPG level was ≥ 11.1 mmol/l (≥ 200 mg/dl). Therapy with OAD was continued at the stable baseline regimen. The primary efficacy endpoint was change in haemoglobin A_1c (HbA_1c) from baseline to endpoint in the intention-to-treat population. Results: At baseline, therapy with OAD was a sulphonylurea only and a sulphonylurea + a biguanide in approximately 24 and 76% of patients respectively. Both glulisine groups had larger reductions in adjusted mean HbA_1c than the OAD-only group (glulisine + OAD, -2.07%; glulisine monotherapy, -1.25%; OAD only, -0.61%). Superiority of glulisine + OAD and glulisine monotherapy vs. OAD only was shown by differences in adjusted mean HbA_1c change from baseline values of -1.46% (p < 0.0001) and -0.64% (p < 0.0001) respectively. Both glulisine groups had better 2h-PPG control than the OAD-only group. Mean daily glulisine doses increased from baseline to endpoint (glulisine + OAD, 13.3-22.5 U; glulisine monotherapy, 14.2-38.0 U). The rate of all symptomatic hypoglycaemia events per patient-year in the entire treatment phase was 11.9 in the glulisine + OAD group, 8.8 in the glulisine monotherapy group and 1.7 in the OAD-only group. There was only one event of severe hypoglycaemia, which occurred in the glulisine + OAD group. Efficacy and safety were similar in Japanese and Korean subpopulations. Conclusions: Both glulisine + OAD and glulisine monotherapy were well tolerated and effective for Japanese and Korean patients with T2DM mellitus inadequately controlled by OAD therapy alone.