The optimal morning: Evening ratio in total dose of twice-daily biphasic insulin analogue in poorly controlled Type 2 diabetes: A 24-week multi-centre prospective, randomized controlled, open-labelled clinical study

Aims: Biphasic insulin analogues are widely used in patients with Type 2 diabetes mellitus suboptimally controlled on oral anti-diabetic drugs. Several topics in this area remain controversial, including how to divide the daily dose of biphasic insulin analogue. We aimed to determine the optimal dosing ratio of twice-daily biphasic insulin analogue and to compare the glycaemic efficacy among groups of patients using different initial dosing ratios of biphasic insulin analogue. Methods: A total of 100 poorly controlled insulin-naive subjects with Type 2 diabetes [HbA_1c ≥ 58 mmol/mol, (7.5%)] on oral anti-diabetic drugs were randomized into three groups according to initial morning:evening dosing ratio (group I, 50:50; group II, 55:45; group III, 60:40) of twice-daily biphasic insulin analogue (biphasic insulin aspart 70/30, biphasic insulin aspart 30). The primary outcome measure was the difference in pre-breakfast to pre-dinner dose ratio at the end of the study. Results: Twice-daily biphasic insulin analogue showed a significant improvement in glycaemic control [HbA_1c from 70 mmol/mol (8.6%) to 60 mmol/mol (7.6%)] after 24 weeks regardless of the initial dose ratio given. Despite the similar efficacy and safety profiles among three groups, morning dose was significantly increased (from 50:50 to 55:45-60:40) in group I after 24 weeks. However, there was no significant change in splitting ratio in groups II and III (with higher morning dose) over the 24-week treatment period. Conclusions: These results indicate that initiating twice-daily biphasic insulin analogue on regimens with a higher dose before breakfast than before dinner (i.e. ratio approximately 55:45 to 60:40) might be more appropriate in Korean subjects with Type 2 diabetes.