title: The combination of DPP-4 inhibitors versus sulfonylureas with metformin after failure of first-line treatment in the risk for major cardiovascular events and death.
abstract: OBJECTIVE
  To determine whether the combination of dipeptidyl-peptidase 4 (DPP-4) inhibitors vs. sulfonylureas with metformin after failure of first-line treatment is associated with a decreased risk for major adverse cardiovascular events (myocardial infarction and stroke) and for all-cause mortality.
  
  
  METHODS
  Using the UK Clinical Practice Research Datalink, a cohort of patients newly treated with metformin or sulfonylurea monotherapy between January 1, 1988, and December 31, 2011, was identified and was followed until December 31, 2012. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to compare the DPP-4 inhibitor-metformin combination to the sulfonylurea-metformin combination so as to study the risk for a composite endpoint consisting of myocardial infarction, stroke and all-cause mortality. The models were adjusted for high-dimensional propensity score deciles.
  
  
  RESULTS
  The cohort consisted of 11,807 patients that included 2286 on a DPP-4 inhibitor-metformin combination and 9521 on a sulfonylurea-metformin combination. The crude incidence rates (95% CIs) of the composite endpoint were 1.2% (0.8% to 1.7%) and 2.2% (1.9% to 2.5%) per year for the DPP-4 inhibitor-metformin and sulfonylurea-metformin combinations, respectively. In the high-dimensional propensity score-adjusted model, the use of the DPP-4 inhibitor-metformin combination was associated with a 38% decreased risk for the composite endpoint (adjusted HR: 0.62; 95% CI 0.40 to 0.98), compared with the sulfonylurea-metformin combination.
  
  
  CONCLUSIONS
  The use of a DPP-4 inhibitor combination with metformin, compared with a sulfonylurea-metformin combination, was associated with decreased risks for major cardiovascular events and all-cause mortality.
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Division of Endocrinology, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Oriana Hoi Yun
authors.initials: OH
authors.lastname: Yu
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.
authors.forename: Hui
authors.initials: H
authors.lastname: Yin
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Department of Oncology, McGill University, Montreal, Quebec, Canada. Electronic address: laurent.azoulay@mcgill.ca.
authors.forename: Laurent
authors.initials: L
authors.lastname: Azoulay
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000150:complications* / Q000517:prevention & control; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000517:prevention & control; D016016:Proportional Hazards Models; D018570:Risk Assessment; D020521:Stroke / Q000150:complications / Q000517:prevention & control; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D013453:Sulfonylurea Compounds; D008687:Metformin
keywords: all-cause mortality; cardiovascular outcomes; mortalité toutes causes confondues; pharmacoepidemiology; pharmacoépidémiologie; résultats cardiovasculaires; traitement du diabète de type 2; type 2 diabetes treatment