Association between dipeptidyl peptidase-4 inhibitors and increased risk for bullous pemphigoid within 3 months from first use: A 5-year Population-Based Cohort Study Using the Japanese National Database.

Aim We assessed the association between dipeptidyl peptidase-4 inhibitors (DPP-4i) and bullous pemphigoid (BP) and time-dependent changes in the risk for developing BP following DPP-4i initiation. Materials and methods The present population-based, real-world study was conducted using the Japanese National Database (NDB) dataset collected between 2013 and 2018. To assess independent correlations between DPP-4i and development of BP, the self-controlled case series method was used. Results Among the cohort followed up for a median of 1540 days, 53,027 patients were likely to develop BP. The possible incidence rate of BP in all 150,328,339 patients was 10.4/100,000 person-years. Among the 9,705,814 patients with type 2 diabetes, 15,634 were likely to develop BP. The possible incidence rate of BP in patients with type 2 diabetes was 38.1/100,000 person-years, while that in patients with type 2 diabetes who did and did not use DPP-4i was 40.7 and 30.0 /100,000 person-years, respectively. Analysis of the 28,705 patients with type 2 diabetes likely to develop BP after initial DPP-4i use revealed a risk ratio of 2.15 (95% CI, 1.75-2.63), 1.70 (95% CI, 1.37-2.11), 1.44 (95% CI, 1.15-1.82), 1.25 (95% CI, 0.98-1.59), 0.84 (95% CI, 0.63-1.10), 0.84 (95% CI, 0.64-1.11), and 1.05 (95% CI, 0.92-1.20), for the risk period of ≤30, 31-60, 61-90, 91-120, 121-150, 151-180, and 181-365 days, respectively. Conclusions Although DPP-4i were associated with increased risk for BP, the risk was particularly significant within 3 months from first use.