title: Case-control study of second-line therapies for type 2 diabetes in combination with metformin and the comparative risks of myocardial infarction and stroke.
abstract: We conducted a population-based case-control study to assess the myocardial infarction (MI) and stroke risks associated with sulphonylureas and insulin when used in combination with metformin. Cases had type 2 diabetes and used metformin + insulin or metformin + sulphonylureas at the time of a first MI or first stroke between 1995 and 2010; controls used the same treatment combinations and were randomly sampled from the same population. MI and stroke diagnoses and potential confounders were validated by medical record reviews. Compared with metformin + sulphonylurea, metformin + insulin was associated with similar risks of MI or stroke [odds ratio 0.98 (95% confidence interval 0.63-1.52)]. Meta-analysis with another observational study improved the precision of the risk estimate [relative risk 0.92 (95% confidence interval 0.69-1.24)]. Current evidence suggests that there may not be large differences in cardiovascular risk associated with the use of insulin or sulphonylureas when used in combination with metformin.
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Floyd
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Wiggins
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Sitlani
authors.affiliation: Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY, USA.|Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Flory
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Seattle, WA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Dublin
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: N L
authors.initials: NL
authors.lastname: Smith
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: S R
authors.initials: SR
authors.lastname: Heckbert
authors.affiliation: Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.|Department of Medicine, University of Washington, Seattle, WA, USA.|Department of Epidemiology, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Seattle, WA, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Psaty
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control; D058065:Diabetic Cardiomyopathies / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008499:Medical Records; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D017410:Practice Guidelines as Topic; D016016:Proportional Hazards Models; D012307:Risk Factors; D020521:Stroke / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology / Q000517:prevention & control*; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D014861:Washington / Q000453:epidemiology
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D008687:Metformin
keywords: cardiovascular outcomes; case-control study; comparative safety; insulin; metformin; myocardial infarction; stroke; sulphonylureas