Purpose
We evaluated the cardiovascular risk associated with dipeptidyl peptidase‐4 inhibitors (DPP‐4Is) as monotherapy compared with other antidiabetic drugs in Japan.
Methods
We conducted a nationwide cohort study involving 2 716 000 diabetes patients in Japan. New users of any antidiabetic drug as monotherapy between 1 April 2010 and 31 October 2014 were identified. Occurrences of myocardial infarction (MI), heart failure (HF), and stroke requiring hospitalization associated with DPP‐4Is were compared with those associated with biguanides (BGs), sulfonylureas (SUs), or α‐glucosidase inhibitors (α‐GIs). Adjusted hazard ratios (aHRs) for these outcomes were estimated by Cox proportional hazards model. Propensity score standardization was used to control for confounding.
Results
We identified 1 105 103 patients using DPP‐4Is, 278 280 patients using BGs, 273 449 patients using SUs, and 217 026 patients using α‐GIs. The risks of MI and HF for DPP‐4I users were significantly higher than those for BG users (MI: aHR, 1.48 [95%CI, 1.20‐1.82], HF: aHR, 1.46 [95%CI, 1.31‐1.62]), while significantly lower than those for SU users (MI: aHR, 0.84 [95%CI, 0.72‐0.98], HF: aHR, 0.86 [95%CI, 0.81‐0.92]). The risk of MI for DPP‐4I users was similar to that for α‐GI users, while the risk of HF for DPP‐4I users was slightly higher than for α‐GI users (MI: aHR, 0.98 [95%CI, 0.82‐1.17], HF: aHR, 1.12[95%CI, 1.04‐1.21]).
Conclusions
Risk of MI and HF requiring hospitalization associated with DPP‐4Is as monotherapy was significantly higher than BGs, significantly lower than SUs, and similar to α‐GIs.