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


CONCLUSIONS
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.
St John Fisher College, Rochester, NY, USA UR Medicine, Rochester, NY, USA anagel@sjfc.edu.
Angela K
AK
Nagel
St John Fisher College, Rochester, NY, USA UR Medicine, Rochester, NY, USA.
Nabila
N
Ahmed-Sarwar
St John Fisher College, Rochester, NY, USA.
Paul M
PM
Werner
St John Fisher College, Rochester, NY, USA Anthony L. Jordan Health Center, Rochester, NY, USA.
Gabriela C
GC
Cipriano
Oracle Health Sciences Global Business Unit, Kattendijke, Zeeland Netherlands.
Robbert P
RP
Van Manen
St John Fisher College, Rochester, NY, USA UR Medicine, Rochester, NY, USA.
Jack E
JE
Brown
D016907:Adverse Drug Reaction Reporting Systems; D001499:Bayes Theorem; D016208:Databases, Factual; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000139:chemically induced*; D014481:United States; D014486:United States Food and Drug Administration
D054873:Dipeptidyl-Peptidase IV Inhibitors
adverse drug reaction; dipeptidyl peptidase-4 inhibitor; disproportionality analysis; oral antihyperglycemic agents; pancreatic carcinoma