Dipeptidyl Peptidase-4 Inhibitor-Associated Pancreatic Carcinoma: A Review of the FAERS Database

Abstract

Background: To date, there is limited literature regarding the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and pancreatic carcinoma.

Objective: To describe the comparative incidence of DPP-4 inhibitors and pancreatic carcinoma as reportedly available in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. The goal was to provide health care practitioners a general understanding of the drug-disease occurrence.

Methods: This is a case/noncase study utilizing Empirica Signal software to query FAERS from November 1968 to December 31, 2013. The software was used to calculate a disproportionality statistic--namely, the empirical Bayesian geometric mean (EBGM)--for reports of DPP-4 inhibitors-associated pancreatic carcinoma. The FDA considers an EBGM significant if the fifth percentile of the distribution is at least 2, defined as an EB05 ≥ 2. With use of a disproportionality analysis, DPP-4 inhibitors were compared with all agents listed in FAERS.

Results: A total of 156 patients experienced pancreatic carcinoma while receiving DPP-4 inhibitor therapy. An EB05 of 10.3 was determined for sitagliptin, 7.1 for saxagliptin, 4.9 for linagliptin, and 1.4 for alogliptin, compared with all other agents included in FAERS. Although an EB05 > 2 was achieved in 2 other antihyperglycemic agents, the findings were not consistent within their medication classes.

Conclusion: There appears to be a statistical association between DPP-4 inhibitor use and pancreatic carcinoma. Causality cannot be inferred from the data provided. Additional clinical studies are needed to further explore this statistical association.

Keywords: adverse drug reaction; dipeptidyl peptidase-4 inhibitor; disproportionality analysis; oral antihyperglycemic agents; pancreatic carcinoma.