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

Background: A recent study is raising concerns that dipeptidyl peptidase 4 inhibitors are associated with increased risk of venous thromboembolism.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.