Assessing Pancreatic Cancer Risk Associated with Dipeptidyl Peptidase 4 Inhibitors: Data Mining of FDA Adverse Event Reporting System (FAERS)
|Xiaodong Feng1 *, Amie Cai3 , Kevin Dong1 , Wendy Chaing1 , Max Feng4 , Nilesh S Bhutada1 , John Inciardi1 and Tibebe Woldemariam2|
|1 Department of Clinical and Administrative Sciences, California Northstate University College of Pharmacy, Rancho Cordova, CA, USA|
|2 Department of Pharmaceutical and Biomedical Sciences, California Northstate University College of Pharmacy, Rancho Cordova, CA, USA|
|3 Department of Molecular & Cell Biology, University of Berkeley, Berkeley, CA, USA|
|4 Rio Americano High School,Carmichael, CA, USA|
|Corresponding Author :||Xiaodong Feng, PharmD, PhD
Department of Clinical and Administrative sciences
California Northstate University College of Pharmacy
Rancho Cordova, CA95670, USA
E-mail: [email protected]
|Received March 25, 2013; Accepted July 23, 2013; Published July 25, 2013|
|Citation: Feng X, Cai A, Dong K, Chaing W, Feng M, et al. (2013) Assessing Pancreatic Cancer Risk Associated with Dipeptidyl Peptidase 4 Inhibitors: Data Mining of FDA Adverse Event Reporting System (FAERS). J Pharmacovigilance 1:110. doi:10.4172/2329-6887.1000110|
|Copyright: © 2013 Feng X, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
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Background: Identifying cancer risks associated with medicinal agents plays an important role in cancer control and prevention. Case reports of cancers associated with pharmacotherapy have been escalating in the Food and Drug Administration Adverse Event Reporting System (FAERS). The objective of this study is to assess the risk of pancreatic cancer associated with anti-diabetic drugs of dipeptidyl peptidase 4 (DPP 4) inhibitors with or without combination of metformin.
Methods: Using the FAERS public database, the adverse event reports (ADRs) associated with widely used DPP 4 inhibitors with or without combination of metformin were generated and evaluated. Standardized pharmacovigilance tools were applied to detect the signal for cancer risks by calculating the proportional reporting ratio (PRR) and the reporting odds ratio (ROR).
Results: Among 12618 ADRs associated with sitagliptin from 2007 to 2011, there were 223 cases of cancer. There was a significant correlation between the cancer reporting ratio and the time (R=0.796, P<0.001). Pancreatic cancers accounted for 22% of all combined cancer adverse events. Pharmacovigilance assessment from 2007 to 2012 indicated that there was a significant risk of pancreatic cancer associated with DPP 4 inhibitors treatment (ROR=5.922). Interestingly, minimal risk of pancreatic cancer risk was associated with metformin (ROR=1.214). Combination of DPP 4 inhibitor sitagliptin with metformin correlates with significantly lower risk of pancreatic cancer compared to sitagliptin treatment without metformin (OR=0.277, 95%CI: 0.210-0.365).
Interpretation: There was a significant signal of pancreatic cancer risk associated with DPP 4 inhibitor treatment. For the first time we demonstrated that combination with metformin significantly reduced the risk signal of pancreatic cancer associated with DPP 4 inhibitors in FAERS. Considering the limitation of the FAERS, this study implied the potential strategy for cancer control and prevention in diabetic patients, and provided directions for future clinical studies.