Trends in Adverse Event Reports of Dipeptidyl Peptidase-4 Inhibitor-Associated Pemphigoid in Japan

Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as a first-line therapy for type 2 diabetes in Japan. Precautions of the package inserts for ethical drugs containing DPP-4 inhibitors were revised for pemphigoid between 2016 and 2018.

This is a retrospective study that investigated the number of DPP-4 inhibitor-associated pemphigoid events using the Japanese Adverse Drug Event Report and its estimated annual incidence rate using a nationwide claims database to assess the trend in reported DPP-4 inhibitor-associated pemphigoid events after the release of the revised precautions in Japan.

We identified 2175 DPP-4 inhibitor-associated pemphigoid events in 2069 case reports. The most common suspected DPP-4 inhibitor was vildagliptin (45.3%), followed by teneligliptin (17.5%), sitagliptin (16.0%), and linagliptin (11.0%). The number of DPP-4 inhibitor-associated pemphigoid events increased from 30 in 2015 to 373 in 2016, reaching a peak of 412 in 2018. Although the estimated annual incidence rate did not exceed 50 per 1,000,000 patients mostly, it exceeded 100 per 1,000,000 for vildagliptin in 2016 and 2018.

The number of reported DPP-4 inhibitor-associated pemphigoid events increased after the revised precautions of package inserts for DPP-4 inhibitors were released.