title: Adding glucose-lowering agents delays insulin initiation and prolongs hyperglycemia.
abstract: Nine classes of glucose-lowering agents (GLAs) are available for patients with type 2 diabetes prior to starting insulin. This study's aim was to determine if the number of GLAs is associated with a difference in glycated hemoglobin (A1C) at insulin initiation in the US Department of Veterans Affairs Health Care System (VAHCS).
  
  
  
  Retrospective cohort study.
  
  
  
  A retrospective cohort with national Veterans Health Administration data was created. Veterans with type 2 diabetes and first insulin prescription filled in the VAHCS between January 1, 2009, and August 28, 2013, were identified. Included veterans refilled insulin within the first year, had an A1C > 7% (53 mmol/mol) at least 60 days prior to insulin initiation, and received a GLA within 6 months prior to insulin. Veterans were grouped into 4 cohorts according to the number of GLAs used.
  
  
  
  A total of 90,497 veterans with type 2 diabetes met inclusion criteria. Insulin was initiated at a mean A1C of 9.9% (85 mmol/mol). The mean A1Cs prior to insulin for 1, 2, 3, or > 3 GLAs were 10.3% (89 mmol/mol), 9.9% (85 mmol/mol), 9.6% (81 mmol/mol), and 9.6% (81 mmol/mol), respectively. Months to insulin increased with the number of GLA trials and prolonged the time veterans were exposed to A1C > 8% (64 mmol/mol).
  
  
  
  Multiple glucose-lowering drug classes are associated with a numerical, but not a clinical, difference in A1C at insulin initiation in the closed formulary of the VAHCS.
authors.affiliation: Kaiser Permanente, 20700 Ventura Blvd, Woodland Hills, CA 91364. E-mail: courtney.hugie@kp.org.
authors.forename: Courtney
authors.initials: C
authors.lastname: Hugie
authors.forename: Nancee V
authors.initials: NV
authors.lastname: Waterbury
authors.forename: Bruce
authors.initials: B
authors.lastname: Alexander
authors.forename: Robert F
authors.initials: RF
authors.lastname: Shaw
authors.forename: Jason A
authors.initials: JA
authors.lastname: Egge
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects*; D015331:Cohort Studies; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis / Q000187:drug effects*; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy*; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014481:United States; D014493:United States Department of Veterans Affairs
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin