Objective: Bullous pemphigoid (BP) is the most common autoimmune blistering skin disorder with unclear etiology. Previous reports showed that BP may be associated with the use of some drugs. This study aimed to evaluate the risk factors for the development of BP and the relationship of BP with the administration of DPP-4i in patients with type 2 diabetes mellitus (T2DM).

Research Design and Methods: Using the National Health Insurance Research Database (NHIRD) from 2009 to 2013, there were 87,029 patients with T2DM. We excluded patients with T2DM without taking any antidiabetic agents and the development of BP before the use of DPP-4i or before they were selected. We identified individuals with T2DM and the use of DPP-4i 84 days or greater as a DPP-4i cohort and subjects never use DPP-4i as a control cohort. They were frequency matched on gender and age within 5 years at a ratio of 1:2.

Results: We identified 14,178 individuals taking DPP-4i and 28,374 matched cohorts without taking DPP-4i. There were 17 BP events in control cohort and 15 BP events in DPP-4i cohort. The incidence of BP was higher in DPP-4i cohort than in control cohort (1.41 vs. 0.59 per 1000 person-years; adjusted HR 2.14, 95% CI = 1.02-4.50). Patients with dementia had a higher associated risk to develop BP (adjusted HR 3.55, 95% CI = 1.30-9.66). The associated risk was lower in patients taking metformin (adjusted HR 0.38, 95% CI = 0.18-0.79) and higher in patients taking spironolactone (adjusted HR 3.06, 95% CI = 1.25-7.51). The cumulative incidence of BP in DPP-4i cohort was higher than in control cohort (log-rank test, p = 0.01).

Conclusion: DPP-4 inhibitors were associated with an increased risk of the development of BP in patients with T2DM. Patients with dementia and taking spironolactone had a higher associated risk. The development of BP in metformin users is significantly lower than in metformin non-user.


J. Guo: None. H. Chen: None. Y. Yang: None. C. Chen: None.

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