title: Progression to treatment failure among Chinese patients with type 2 diabetes initiated on metformin versus sulphonylurea monotherapy--The Hong Kong Diabetes Registry.
abstract: OBJECTIVE
  To assess the development of treatment failure in Chinese patients with type 2 diabetes mellitus (T2DM) initiated on metformin or sulphonylurea (SU) monotherapy, with consideration of various potential sources of biases.
  
  
  METHODS
  A 1:1-matched new metformin and SU user cohort on immortal time and mean propensity score after multiple imputation was selected from a cohort of 5889 Chinese patients with T2DM. Treatment failure was defined as progression to (i) combination oral anti-hyperglycemia drug therapy, (ii) insulin use, or (iii) a treatment haemoglobin A1c (HbA1c) >7.5% (58 mmol/mol). Stratified Cox regression analysis on the matched pairs was employed to examine the associations between initial monotherapy and onset of treatment failure.
  
  
  RESULTS
  Of 554 new metformin and 840 new SU users, 380 were matched. During a median follow-up duration of 3 years, 173 (45.6%) metformin users and 220 (57.9%) SU users experienced treatment failure (annual failure rates of 15% and 19%, respectively). The median time from monotherapy starting to treatment failure was 3.0 [inter-quartile range (IQR): 1.8-5.4] years for metformin users, versus 1.8 (IQR: 0.9-4.1) years for SU users (p<0.001). Stratified Cox regression analysis showed significantly lower risk of treatment failure for metformin users (HR [95% CI], 0.62[0.47-0.81]; p<0.001). Consistent results were found in analyses based on traditional adjustment schemes with or without imputation.
  
  
  CONCLUSIONS
  By systematically incorporating new-user design, multiple imputation and matching methods, we found that Chinese patients with T2DM initiated on metformin monotherapy were associated with a significant delay in the onset of treatment failure compared to SU monotherapy.
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Guozhi
authors.initials: G
authors.lastname: Jiang
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Andrea O
authors.initials: AO
authors.lastname: Luk
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Tianjin Medical University, Tianjin, China.
authors.forename: Xilin
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Claudia H T
authors.initials: CHT
authors.lastname: Tam
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Siu Him
authors.initials: SH
authors.lastname: Lau
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Risa
authors.initials: R
authors.lastname: Ozaki
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, Hong Kong; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Alice P S
authors.initials: APS
authors.lastname: Kong
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Tong
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Chun Chung
authors.initials: CC
authors.lastname: Chow
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, Hong Kong; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong.
authors.forename: Juliana C N
authors.initials: JCN
authors.lastname: Chan
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong. Electronic address: wingyeeso@cuhk.edu.hk.
authors.forename: Wing Yee
authors.initials: WY
authors.lastname: So
authors.affiliation: Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, Hong Kong; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, Hong Kong; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong. Electronic address: rcwma@cuhk.edu.hk.
authors.forename: Ronald C W
authors.initials: RCW
authors.lastname: Ma
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006723:Hong Kong / Q000453:epidemiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D010045:Outpatients; D057216:Propensity Score; D012042:Registries; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D013997:Time Factors; D017211:Treatment Failure
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D013453:Sulfonylurea Compounds
keywords: Diabetes; Drug use bias; Metformin; Sulphonylurea; Treatment failure