title: Capitalizing on prescribing pattern variation to compare medications for type 2 diabetes.
abstract: BACKGROUND
  Clinical trials often compare hypoglycemic medications on the basis of glycemic control but do not examine long-term outcomes (e.g., mortality). This study demonstrates an alternative approach to lengthening clinical trials to assess these long-term outcomes.
  
  
  OBJECTIVE
  To use observational quasi-experimental methods using instrumental variables (IVs) to compare the effect of two hypoglycemic medications, sulfonylureas (SUs) and thiazolidinediones (TZDs), on long-term outcomes.
  
  
  METHODS
  This study used administrative data from the Veterans Health Administration and Medicare from 2000 to 2010. The study population included US veterans dually enrolled in Medicare who received a prescription for metformin and then initiated SUs or TZDs. Patients could either continue on or discontinue metformin after the initiation of the second agent. Treatment was defined as starting either a SU or a TZD. Local variations in SU prescribing rates were used as instruments in IV models to control for selection bias. Survival models predicted all-cause mortality, ambulatory care sensitive condition hospitalizations, and stroke or heart attack (acute myocardial infarction).
  
  
  RESULTS
  Starting on SUs compared to TZDs significantly increased the likelihood of experiencing mortality and ACSC hospitalization. The estimated hazard ratio for the effect of starting on SUs compared to TZDs was 1.50 (95% confidence interval [CI] 1.09-2.09) for all-cause mortality, 1.68 (95% CI 1.31-2.15) for ambulatory care sensitive condition hospitalization, and 1.15 (95% CI 0.80-1.66) for acute myocardial infarction or stroke.
  
  
  CONCLUSIONS
  Our findings suggest increased risk of major adverse events associated with SUs as a second-line agent. Quasi-experimental IV methods may be an important alternative to lengthening clinical trials to assess long-term outcomes.
authors.affiliation: VA Boston Healthcare System, Boston, MA; Boston University School of Medicine, Boston, MA. Electronic address: jprentic@bu.edu.
authors.forename: Julia C
authors.initials: JC
authors.lastname: Prentice
authors.affiliation: VA Boston Healthcare System, Boston, MA; Harvard Medical School, Harvard University, Boston, MA.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Conlin
authors.affiliation: VA Pittsburgh Medical Center, Pittsburgh, PA; University of Pittsburgh, Pittsburgh, PA.
authors.forename: Walid F
authors.initials: WF
authors.lastname: Gellad
authors.affiliation: Durham VA Medical Center, Durham, NC; Duke University School of Medicine, Duke University, Durham, NC.
authors.forename: David
authors.initials: D
authors.lastname: Edelman
authors.affiliation: University of Illinois at Chicago, Chicago, IL.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Lee
authors.affiliation: VA Boston Healthcare System, Boston, MA; Northeastern University, Boston, MA.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Pizer
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality; D004359:Drug Therapy, Combination; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D006278:Medicare; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D014481:United States; D014493:United States Department of Veterans Affairs
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D008687:Metformin
keywords: comparative effectiveness research; instrumental variables; provider-prescribing variation; type 2 diabetes