ObjectivesThe elderly (aged ≥65 years) population with type 2 diabetes (T2D) is growing substantially, but evidence for associations between the use of dipeptidyl peptidase-4 inhibitors (DPP-4is), novel incretin-based antidiabetic drugs, and clinical hard endpoints in this group remains inconclusive. We aimed to assess the safety and cardiovascular effects of DPP-4i use in a nationally representative sample of elderly adults with T2D. Design, setting, and participantsWe conducted a nationwide, observational, propensity score–matched study using Taiwan's National Health Insurance Research Database. Of a total of 414,213 patients aged ≥65 years with T2D, 58,485 patients receiving initial DPP-4i prescriptions between March 1, 2009, and June 31, 2013, were included. Each DPP-4i user was matched with a nonuser control using propensity scores. The endpoints were all-cause mortality and major adverse cardiovascular events (MACEs), including ischemic stroke and myocardial infarction. Potential adverse effects of hospitalization for heart failure and hypoglycemia were also evaluated. ResultsCompared with the matched control cohort, the risks of all-cause mortality (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.52–0.56), MACEs (HR 0.79, 95% CI 0.75–0.83), myocardial infarction (HR 0.79, 95% CI 0.72–0.87), and ischemic stroke (HR 0.79, 95% CI 0.75–0.84) were lower in the DPP-4i cohort. DPP-4i use did not affect the risks of hospitalization for heart failure and hypoglycemia. Stratified analyses produced consistent results across age, sex, and comorbidity subgroups. ConclusionsPrescription of DPP-4is was associated with reduced risks of all-cause mortality and MACEs in patients aged ≥65 years with T2D.