title: All-cause mortality and cardiovascular effects associated with the DPP-IV inhibitor sitagliptin compared with metformin, a retrospective cohort study on the Danish population.
abstract: OBJECTIVE
  We performed a retrospective cohort study, investigating the clinical outcomes including mortality and cardiovascular disease of sitagliptin compared with metformin monotherapies.
  
  
  METHODS
  All patients receiving monotherapy with the dipeptidyl peptidase-IV inhibitors (DPP-IV) inhibitor sitagliptin between 1 January 2007 and 31 December 2011 were identified. All-cause mortality and a composite endpoint of stroke, acute myocardial infarction (AMI) and all-cause mortality associated with sitagliptin monotherapy were compared with metformin monotherapy. In addition, as an indicator of efficacy we analysed the hazard ratio of changing treatment.
  
  
  RESULTS
  A total of 84 756 patients were included in the analysis, 1228 (1.4%) received sitagliptin monotherapy whereas the remaining 83 528 (98.6%) patients received metformin monotherapy. Patients using metformin were younger than patients using sitagliptin (59.0 ± 15.2 vs. 62.5 ± 13.1) were less often male (51.6 vs. 54.2%) and had longer treatment duration with monotherapy (1.8 ± 1.3 vs. 0.9 ± 1.1 years). Compared with patients receiving metformin, patients using sitagliptin showed no statistically significant excess risks of all-cause mortality [hazard ratio, 1.25; 95% confidence interval (CI), 0.92-1.71; p = 0.153] or the composite endpoint (hazard ratio, 1.22; 95% CI, 0.92-1.61; p = 0.164). However, the use of sitagliptin monotherapy was associated with an increased likelihood of changing treatment (hazard ratio, 4.88; 95% CI, 4.46-5.35; p < 0.001).
  
  
  CONCLUSIONS
  In a retrospective analysis, sitagliptin monotherapy compared with metformin monotherapy was not associated with any statistical significant increased risk of all-cause mortality or the composite endpoint, but was associated with an increased likelihood of changing glucose-lowering treatment.
authors.affiliation: Institute of Health, Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: N M
authors.initials: NM
authors.lastname: Scheller
authors.forename: U M
authors.initials: UM
authors.lastname: Mogensen
authors.forename: C
authors.initials: C
authors.lastname: Andersson
authors.forename: A
authors.initials: A
authors.lastname: Vaag
authors.forename: C
authors.initials: C
authors.lastname: Torp-Pedersen
mesh_terms: D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000097:blood / Q000401:mortality*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000401:mortality*; D016016:Proportional Hazards Models; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D012189:Retrospective Studies; D000068900:Sitagliptin Phosphate; D020521:Stroke / Q000097:blood / Q000401:mortality*; D016896:Treatment Outcome; D014230:Triazoles / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011719:Pyrazines; D014230:Triazoles; D008687:Metformin; D000068900:Sitagliptin Phosphate
keywords: DPP-IV inhibitors; acute myocardial infarction; all-cause mortality; metformin monotherapy; sitagliptin monotherapy; stroke; treatment efficacy