Dipeptidyl peptidase-4 inhibitors and risk of venous thromboembolism: data mining of FDA adverse event reporting system.

A recent study is raising concerns that dipeptidyl peptidase 4 inhibitors are associated with increased risk of venous thromboembolism. We aimed to assess the association between dipeptidyl peptidase-4 inhibitors and venous thromboembolism using the US Food and Drug Administration Adverse Event Reporting System database. We searched the venous thromboembolism cases related to dipeptidyl peptidase-4 inhibitors from 2004 first quarter to 2018 first quarter. We compared dipeptidyl peptidase-4 inhibitors versus three groups: (1) all other glucose-lowering drugs excluding insulins; (2) sulfonylureas and sodium–glucose-cotransporter-2 inhibitors; (3) sodium–glucose-cotransporter-2 inhibitors. In each comparison, we calculated proportional rate ratios and 95% confidence ratios by SAS 9.4. We obtained 873 dipeptidyl peptidase-4 inhibitors-associated venous thromboembolism events. Compared to all other glucose lowering-drugs excluding insulins, the proportional reporting ratio for overall venous thromboembolism, deep vein thrombosis, pulmonary embolism were 0.92 (0.86, 0.99), 0.91 (0.82,1.01), and 0.82 (0.74,0.90), respectively; the proportional reporting ratio for portal vein thrombosis, splenic vein thrombosis, mesenteric vein thrombosis were 3.94 (2.96, 5.25), 10.80 (6.14, 18.99), and 4.98 (2.76,8.96), respectively. Our analysis found no association between dipeptidyl peptidase-4 inhibitors and venous thromboembolism risk, while moderate to strong signals of portal vein thrombosis, splenic vein thrombosis, mesenteric vein thrombosis risks were observed.