Cardiovascular Outcomes of Dipeptidyl Peptidase-4 Inhibitors in Elderly Patients With Type 2 Diabetes: A Nationwide Study

J Am Med Dir Assoc. 2016 Jan;17(1):59-64. doi: 10.1016/j.jamda.2015.10.009. Epub 2015 Nov 21.


Objectives: The 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 participants: We 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.

Results: Compared 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.

Conclusions: Prescription of DPP-4is was associated with reduced risks of all-cause mortality and MACEs in patients aged ≥65 years with T2D.

Keywords: Dipeptidyl peptidase-4 inhibitor; diabetes mellitus; elderly; major adverse cardiovascular events; mortality.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Heart Failure / epidemiology
  • Hospitalization / statistics & numerical data
  • Humans
  • Hypoglycemia / epidemiology
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Medication Adherence
  • Myocardial Infarction / epidemiology*
  • Propensity Score
  • Stroke / epidemiology*
  • Taiwan / epidemiology


  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents