All-cause mortality and cardiovascular effects associated with the DPP-IV inhibitor sitagliptin compared with metformin, a retrospective cohort study on the Danish population

Aim 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