title: Comparative Effectiveness of Insulin versus Combination Sulfonylurea and Insulin: a Cohort Study of Veterans with Type 2 Diabetes.
abstract: Type 2 diabetes patients often initiate treatment with a sulfonylurea and subsequently intensify their therapy with insulin. However, information on optimal treatment regimens for these patients is limited.
  
  
  
  To compare risk of cardiovascular disease (CVD) and hypoglycemia between sulfonylurea initiators who switch to or add insulin.
  
  
  
  This was a retrospective cohort assembled using national Veterans Health Administration (VHA), Medicare, and National Death Index databases.
  
  
  
  Veterans who initiated diabetes treatment with a sulfonylurea between 2001 and 2008 and intensified their regimen with insulin were followed through 2011.
  
  
  
  The association between insulin versus sulfonylurea + insulin and time to CVD or hypoglycemia were evaluated using Cox proportional hazard models in a 1:1 propensity score-matched cohort. CVD included hospitalization for acute myocardial infarction or stroke, or cardiovascular mortality. Hypoglycemia included hospitalizations or emergency visits for hypoglycemia, or outpatient blood glucose measurements <60 mg/dL. Subgroups included age < 65 and ≥ 65 years and estimated glomerular filtration rate ≥ 60 and < 60 ml/min.
  
  
  
  There were 1646 and 3728 sulfonylurea monotherapy initiators who switched to insulin monotherapy or added insulin, respectively. The 1596 propensity score-matched patients in each group had similar baseline characteristics at insulin initiation. The rate of CVD per 1000 person-years among insulin versus sulfonylurea + insulin users were 49.3 and 56.0, respectively [hazard ratio (HR) 0.85, 95 % confidence interval (CI) 0.64, 1.12]. Rates of first and recurrent hypoglycemia events per 1000 person-years were 74.0 and 100.0 among insulin users compared to 78.9 and 116.8 among sulfonylurea plus insulin users, yielding HR (95 % CI) of 0.94 (0.76, 1.16) and 0.87 (0.69, 1.10), respectively. Subgroup analysis results were consistent with the main findings.
  
  
  
  Compared to sulfonylurea users who added insulin, those who switched to insulin alone had numerically lower CVD and hypoglycemia events, but these differences in risk were not statistically significant.
authors.affiliation: Veterans Health Administration - Tennessee Valley Healthcare System Geriatrics Research Education Clinical Center (GRECC), Health Service Research and Development Center (HSRD), Nashville, TN, USA.|Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Jea Young
authors.initials: JY
authors.lastname: Min
authors.affiliation: Veterans Health Administration - Tennessee Valley Healthcare System Geriatrics Research Education Clinical Center (GRECC), Health Service Research and Development Center (HSRD), Nashville, TN, USA.|Department of Medicine, Vanderbilt University, Nashville, TN, USA.|Department of Health Policy, Vanderbilt University, Nashville, TN, USA.
authors.forename: Marie R
authors.initials: MR
authors.lastname: Griffin
authors.affiliation: Veterans Health Administration - Tennessee Valley Healthcare System Geriatrics Research Education Clinical Center (GRECC), Health Service Research and Development Center (HSRD), Nashville, TN, USA.|Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Adriana M
authors.initials: AM
authors.lastname: Hung
authors.affiliation: Veterans Health Administration - Tennessee Valley Healthcare System Geriatrics Research Education Clinical Center (GRECC), Health Service Research and Development Center (HSRD), Nashville, TN, USA.|Department of Health Policy, Vanderbilt University, Nashville, TN, USA.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Grijalva
authors.affiliation: Veterans Health Administration - Tennessee Valley Healthcare System Geriatrics Research Education Clinical Center (GRECC), Health Service Research and Development Center (HSRD), Nashville, TN, USA.|Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Greevy
authors.affiliation: Veterans Health Administration - Tennessee Valley Healthcare System Geriatrics Research Education Clinical Center (GRECC), Health Service Research and Development Center (HSRD), Nashville, TN, USA.|Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
authors.forename: Xulei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Veterans Health Administration - Tennessee Valley Healthcare System Geriatrics Research Education Clinical Center (GRECC), Health Service Research and Development Center (HSRD), Nashville, TN, USA.|Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Tom
authors.initials: T
authors.lastname: Elasy
authors.affiliation: Veterans Health Administration - Tennessee Valley Healthcare System Geriatrics Research Education Clinical Center (GRECC), Health Service Research and Development Center (HSRD), Nashville, TN, USA. christianne.roumie@vanderbilt.edu.|Department of Medicine, Vanderbilt University, Nashville, TN, USA. christianne.roumie@vanderbilt.edu.
authors.forename: Christianne L
authors.initials: CL
authors.lastname: Roumie
mesh_terms: D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000453:epidemiology; D015331:Cohort Studies; D057186:Comparative Effectiveness Research / Q000379:methods; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D057915:Drug Substitution; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D014481:United States / Q000453:epidemiology; D014728:Veterans
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds
keywords: cardiovascular disease; comparative effectiveness; diabetes mellitus; hypoglycemia; insulin; sulfonylurea