Association between dipeptidyl peptidase-4 inhibitor and aspiration pneumonia: disproportionality analysis using the spontaneous reporting system in Japan

Purpose Dipeptidyl peptidase-4 inhibitor (DPP-4-Is), a kind of drug used for the treatment of diabetes, is considered to prevent the degradation of substance P that suppresses the occurrence of dysphagia. On the other hand, DPP-4 inhibitors are also known to act on the immune system. In this study, we used a spontaneous reporting system to evaluate the signals for dysphagia and aspiration pneumonia with DPP-4-Is. Methods We calculated reporting odds ratio ( ROR ) and information coefficients ( IC ) as disproportionality analysis to evaluate DPP-4-Is induced dysphagia and aspiration pneumonia using the Japanese Adverse Drug Event Report (JADER) database. Results For DPP-4-Is as a class, no signals were detected for dysphagia, but the signal for aspiration pneumonia was detected at ROR 1.67 (95% confidence interval [95% CI]: 1.20 to 2.34) and IC 0.70 (95% CI: 0.21 to 1.19). For aspiration pneumonia, trelagliptin was the only drug among the DPP-4-Is for which both ROR and IC signals were detected ( ROR 9.99, 95% CI: 4.10 to 24.36; IC : 1.98, 95% CI: 0.78 to 3.18). ROR signals, but not IC signals, were detected for linagliptin ( ROR 2.66, 95% CI: 1.19 to 5.94; IC : 1.09, 95% CI: − 0.004 to 2.19) and sitagliptin ( ROR 1.84, 95% CI: 1.04 to 3.25; IC : 0.78, 95% CI: − 0.03 to 1.58). Conclusion Since DPP-4 inhibitors prevent the degradation of substance P involved in swallowing reflex, DPP-4 inhibitors were expected to prevent dysphagia and aspiration pneumonia. However, this study revealed that DPP-4 inhibitors strongly were associated with onset rather than preventing aspiration pneumonia. This result suggests that DPP-4 inhibitors may affect the immune function associated with the development of aspiration pneumonia. Furthermore, there is a possibility that the amount of DPP-4-Is used clinically cannot increase the amount of substance P in sufficient quantity to prevent aspiration pneumonia.