title: Comparative risk for cardiovascular diseases of dipeptidyl peptidase-4 inhibitors vs. sulfonylureas in combination with metformin: Results of a two-phase study.
abstract: The aim was to assess whether the use of additional data from the Disease Management Program (DMP) diabetes mellitus type 2 to minimize the potential for residual confounding will alter the estimated risk of either myocardial infarction, ischemic stroke or heart failure in patients with type 2 diabetes using sulfonylureas compared to dipeptidyl peptidase-4 (DPP-4) inhibitors in addition to metformin based on routine health care data.
  
  
  
  We conducted a nested two-phase case-control study using claims data of one German health insurance from 2004 to 2013 (phase 1) and data of the DMP from 2010 to 2013 (phase 2). Adjusted odds ratios (ORs) for the combined cardiovascular event myocardial infarction, ischemic stroke or heart failure were calculated using a two-phase logistic regression.
  
  
  
  Phase 1 comprised 3179 patients (289 cases; 2890 controls) and phase 2 comprised 1968 patients (168 cases; 1800 controls). We observed an adjusted OR of 0.83 for the combined cardiovascular event (95% CI: 0.61-1.13).
  
  
  
  We observed a non-significantly reduced risk for cardiovascular diseases in patients using DPP-4 inhibitors compared to sulfonylureas in addition to metformin. This finding was not altered by the inclusion of additional information of the DMP in the analysis. However, due to the low power of this study, further studies are needed to reproduce our findings.
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology-BIPS, Bremen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Enders
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology-BIPS, Bremen, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Kollhorst
authors.affiliation: Scientific Institute of TK for Benefit and Efficiency in Health Care, Hamburg, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Engel
authors.affiliation: Scientific Institute of TK for Benefit and Efficiency in Health Care, Hamburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Linder
authors.affiliation: Scientific Institute of TK for Benefit and Efficiency in Health Care, Hamburg, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Verheyen
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology-BIPS, Bremen, Germany. Electronic address: pigeot@leibniz-bips.de.
authors.forename: Iris
authors.initials: I
authors.lastname: Pigeot
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D008687:Metformin; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
keywords: Adverse drug effects; Combination therapy; Diabetes type 2; Health insurance data; Pharmacoepidemiological research database