title: Kidney function decline in metformin versus sulfonylurea initiators: assessment of time-dependent contribution of weight, blood pressure, and glycemic control.
abstract: OBJECTIVE
  We recently reported that kidney function declined faster among initiators of sulfonylureas compared to metformin; however, sulfonylurea use compared to metformin use was also associated with increases in body mass index (BMI) and systolic blood pressure (SBP). We sought to determine if differences between sulfonylureas and metformin on kidney function decline were mediated by differential effects on BMI, SBP, or glucose control.
  
  
  METHODS
  We identified 13,238 veterans who initiated sulfonylurea or metformin treatment (2000–2007) with a baseline estimated glomerular filtration rate (eGFR) >60 mL/minute, and followed them until a study event occurred, non-persistence on treatment, loss of follow-up, or end of the study. The composite outcome was a sustained decline from baseline eGFR of ≥25%, end-stage renal disease, or death. We estimated the association of cumulative measurements of potential mediators including BMI, SBP, and glycated hemoglobin on the study outcome. We determined if controlling for these time-varying covariates accounted for the differences in outcome between sulfonylurea and metformin initiators.
  
  
  RESULTS
  Compared to sulfonylurea use, metformin use was associated with a lower risk for renal function decline or death [adjusted hazard ratio (aHR) 0.82, 95% confidence interval 0.70, 0.97]. This protective association remained significant [aHR 0.83 (0.70–0.98)] when accounting for the cumulative time-varying measurements of the three mediators of interest.
  
  
  CONCLUSIONS
  Metformin initiation was associated with a lower risk of kidney function decline or death compared to sulfonylureas, which which appeared to be independent of changes in BMI, SBP, and glycated hemoglobin over time.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Hung
authors.forename: Christianne L
authors.initials: CL
authors.lastname: Roumie
authors.forename: Robert A
authors.initials: RA
authors.lastname: Greevy
authors.forename: Xulei
authors.initials: X
authors.lastname: Liu
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Grijalva
authors.forename: Harvey J
authors.initials: HJ
authors.lastname: Murff
authors.forename: Marie R
authors.initials: MR
authors.lastname: Griffin
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008499:Medical Records; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D008875:Middle Aged; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D013997:Time Factors; D014481:United States; D014728:Veterans
chemical_list: D001786:Blood Glucose; D013453:Sulfonylurea Compounds; D008687:Metformin