BACKGROUND: Several antidiabetic drugs (i.e., sulfonylureas; SU, rosiglitazone) 
have been reported to be associated with increased risks of cardiovascular 
diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). Dipeptidyl 
peptidase-4 inhibitors (DPP4i) are newly available antidiabetic drugs. Most 
studies only compared DPP4i with a placebo or SU, or targeted a specific CVD 
event of interest (i.e., heart failure; HF). Comparative research of CVD risks 
of DPP4i with other antidiabetic drugs (i.e., metformin, thiazolidinediones, 
meglitinides, acarbose, and insulin) remains scarce. This study was aimed to 
assess comparative risks of CVD, including ischemic stroke, myocardial 
infarction (MI) and HF, and hypoglycemia of DPP4i with other antidiabetic drugs.
METHODS: We utilized Taiwan's National Health Insurance Research Database. A 
total of 123,050 T2DM patients newly prescribed oral antidiabetic treatments 
were identified in 2009-2010 and followed until 2013. Outcome endpoints included 
a composite of CVD events: hospitalizations for ischemic stroke, MI and HF, and 
hypoglycemia. Time-varying Cox proportional hazards regression was applied to 
assess the time to event hazards of various antidiabetic drugs, adjusted for 
patients' demographics, comorbidity, diabetic complications, and co-medications. 
Additional analyses were performed for the patients with and without CVD 
history, respectively.
RESULTS: DPP4i users had significantly lower CVD risks as compared to that of 
non-DPP4i users (adjusted hazard ratio [aHR]: 0.83, 95 % confidence interval 
[CI]: 0.76-0.91). Compared to DPP4i users, meglitinides (aHR 1.3, 95 % CI 
1.20-1.43) and insulin users (aHR 3.73, 95 % CI 3.35, 4.14) had significantly 
higher risks for composite CVD, as well as those for stroke, MI, HF, and 
hypoglycemia. Additionally, metformin users had significantly lower risks for 
composite CVD risk (aHR 0.87, 95 % CI 0.79-0.94), as well as those for MI, HF, 
and hypoglycemia, as compared to those of DPP4i users. Although there was a 
trend toward low CVD risks in pioglitazone users, the role of potential 
confounding by indication cannot be excluded.
CONCLUSIONS: DPP4i-treated T2DM patients had lower risks for CVD as compared to 
those for non-DPP4i users, except metformin users.