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 [HbA1c ≥ 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 [HbA1c 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. What's new? Although biphasic insulin analogues are widely used in patients with Type 2 diabetes who are suboptimally controlled on oral anti‐diabetic drugs, the optimal dosing ratio of twice‐daily biphasic insulin analogue is currently unknown. Currently, the pre‐breakfast:pre‐dinner ratio of 50:50 is recommended by several clinical guidelines. However, there is a lack of evidence for these starting regimens regarding the dosing split before breakfast and before dinner. This study is, to our best knowledge, the first randomized study that has investigated the optimal dosing ratio of twice‐daily biphasic insulin analogue.