title: 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.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine.
authors.forename: C H
authors.initials: CH
authors.lastname: Jung
authors.forename: J-Y
authors.initials: JY
authors.lastname: Park
authors.forename: J H
authors.initials: JH
authors.lastname: Cho
authors.forename: K-H
authors.initials: KH
authors.lastname: Yoon
authors.forename: H K
authors.initials: HK
authors.lastname: Yang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Lee
authors.forename: B S
authors.initials: BS
authors.lastname: Cha
authors.forename: B-W
authors.initials: BW
authors.lastname: Lee
mesh_terms: D061265:Biphasic Insulins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015190:Blood Glucose Self-Monitoring; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D056910:Republic of Korea; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D061265:Biphasic Insulins; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; C517652:hemoglobin A1c protein, human