title: Case-control study of oral glucose-lowering drugs in combination with long-acting insulin and the risks of incident myocardial infarction and incident stroke.
abstract: BACKGROUND
  The use of oral glucose-lowering therapies with insulin is common, but the cardiovascular effects are largely unknown. Among users of long-acting insulin, we conducted a population-based case-control study to evaluate the incident myocardial infarction (MI) and incident stroke risks associated with the use of sulfonylureas and the use of metformin.
  
  
  METHODS
  Cases were Group Health Cooperative enrollees with type 2 diabetes who used long-acting insulin at the time of diagnosis with a first MI (n = 413) or first stroke (n = 247) from 1995 to 2010. Controls (n = 443) with type 2 diabetes who used long-acting insulin were matched to cases on age, sex, and calendar year. Sulfonylurea and metformin use was classified as current, past, or never using electronic pharmacy records. MI and stroke diagnoses were validated by medical record review. Analyses were adjusted for potential confounders.
  
  
  RESULTS
  Current use of sulfonylureas compared with never use was associated with a higher risk of MI (odds ratio [OR] 1.67; 95% confidence interval [CI], 1.10-2.55) but not stroke (OR 1.22; 95%CI, 0.74-2.00). Current use of metformin compared with never use was associated with a lower risk of stroke (OR 0.54; 95%CI, 0.31-0.95) but not MI (OR 0.77; 95%CI, 0.44-1.33). Past use of sulfonylureas and past use of metformin were not associated with either outcome.
  
  
  CONCLUSIONS
  Sulfonylureas in combination with long-acting insulin may increase the risk of MI compared with the use of insulin alone. Metformin may be an important cardiovascular disease prevention therapy for patients on insulin therapy. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Floyd
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
authors.forename: Kerri L
authors.initials: KL
authors.lastname: Wiggins
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Christiansen
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Seattle, WA, USA.
authors.forename: Sascha
authors.initials: S
authors.lastname: Dublin
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Department of Neurology, University of Washington, Seattle, WA, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Longstreth
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.|Department of Epidemiology, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Seattle, WA, USA.|Seattle Epidemiologic Research and Information Center, Department of Veterans Affairs, Office of Research and Development, Seattle, WA, USA.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.|Department of Biostatistics, University of Washington, Seattle, WA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: McKnight
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.|Department of Epidemiology, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Seattle, WA, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Noel S
authors.initials: NS
authors.lastname: Weiss
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.|Department of Epidemiology, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Seattle, WA, USA.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects; D015994:Incidence; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D013453:Sulfonylurea Compounds; D008687:Metformin
keywords: case-control study; insulin; metformin; myocardial infarction; pharmacoepidemiology; stroke; sulfonylureas