title: Comparison of thrice-daily premixed insulin (insulin lispro premix) with basal-bolus (insulin glargine once-daily plus thrice-daily prandial insulin lispro) therapy in east Asian patients with type 2 diabetes insufficiently controlled with twice-daily premixed insulin: an open-label, randomised, controlled trial.
abstract: BACKGROUND
  Unlike in western countries, premixed insulin is widely used as the starter insulin in Asian patients instead of basal insulin. The use of basal-bolus therapy as an intensification regimen is not common in Asia despite poor glycaemic control after starting insulin therapy. An alternative insulin intensification regimen with a similar efficacy and safety profile to basal-bolus therapy, but of higher convenience, is urgently needed. The efficacy and safety of insulin lispro mix thrice-daily was compared with basal-bolus therapy in Asian patients with type 2 diabetes who were insufficiently controlled on twice-daily premixed insulin.
  
  
  METHODS
  This open-label, randomised, active comparator-controlled, parallel-group trial was done at 24 centres in China, Taiwan, and South Korea. Patients with type 2 diabetes who were inadequately controlled on twice-daily premixed insulin were randomly assigned (1:1) to receive either insulin lispro mix (mix 50 before breakfast and lunch plus mix 25 before dinner) or basal-bolus therapy (insulin glargine at bedtime plus prandial insulin lispro thrice-daily) for 24 weeks. Randomisation was done by a computer-generated random sequence and was stratified by country or region and baseline HbA1c. Treatment assignments were masked from the study team assessing outcomes but not from investigators and patients. The primary outcome was change from baseline in HbA1c at week 24 in all randomly assigned patients who received at least one dose of study drug. Analysis was by modified intention to treat, with the per-protocol population used as a supportive analysis. This study is registered with ClinicalTrials.gov, number NCT01175811.
  
  
  RESULTS
  Between Feb 7, 2011, and Nov 7, 2012, 402 patients were enrolled (199 in the premix group, 203 in the basal-bolus group) and 399 were included in the primary analysis (197 in the premix group, 202 in the basal-bolus group). HbA1c change at week 24 was -1.1% for both treatment groups. The least squares mean difference between groups in HbA1c change from baseline was 0% (95% CI -0.1 to 0.2). Insulin lispro mix was non-inferior to basal-bolus therapy based on the prespecified margin of 0.4%. The frequency of adverse events, and the incidences and 30-day rates of nocturnal and overall hypoglycaemia were comparable between groups. No severe hypoglycaemia was reported.
  
  
  CONCLUSIONS
  A premixed insulin lispro regimen thrice-daily was non-inferior to basal-bolus therapy in terms of overall glycaemic control and thus could be an option for intensified insulin regimen in Asian patients with type 2 diabetes who are inadequately controlled with twice-daily premixed insulin.
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China. Electronic address: wpjia@sjtu.edu.cn.
authors.forename: Weiping
authors.initials: W
authors.lastname: Jia
authors.affiliation: Department of Endocrinology, Peking Union Medical College Hospital, Dongcheng District, Beijing, PR China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Endocrinology, First Affiliated Hospital of Fourth Military Medical University, Xi'an, PR China.
authors.forename: Qiuhe
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Department of Endocrinology, Kyung Hee University Hospital at Gangdong, Seoul, South Korea.
authors.forename: Kyu-Jeung
authors.initials: KJ
authors.lastname: Ahn
authors.affiliation: Internal Medicine Department, National Taiwan University Hospital, Zhongzheng District, Taipei, Taiwan.
authors.forename: Lee-Ming
authors.initials: LM
authors.lastname: Chuang
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Can
authors.initials: C
authors.lastname: Pang
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Yinfang
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Medical Division, Eli Lilly Suzhou Pharmaceuticals Co. Ltd, Shanghai, PR China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Li
authors.affiliation: Medical Division, Eli Lilly Suzhou Pharmaceuticals Co. Ltd, Shanghai, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
mesh_terms: D020909:Acarbose / Q000627:therapeutic use; D000368:Aged; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007294:Inositol / Q000031:analogs & derivatives / Q000627:therapeutic use; D000069036:Insulin Glargine / Q000008:administration & dosage*; D061268:Insulin Lispro / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D056910:Republic of Korea; D013624:Taiwan; D016896:Treatment Outcome
chemical_list: D020909:Acarbose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007294:Inositol; D000069036:Insulin Glargine; D061268:Insulin Lispro; D008687:Metformin; C517652:hemoglobin A1c protein, human; C102817:voglibose