Dipeptidyl Peptidase-4 Inhibitors and the Risk of Bullous Pemphigoid Among Patients With Type 2 Diabetes

OBJECTIVE There are uncertainties regarding the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and bullous pemphigoid (BP), a potentially severe autoimmune skin disease. Thus, we conducted a population-based study to determine whether use of DPP-4 inhibitors, when compared with other second- to third-line antidiabetic drugs, is associated with an increased risk of BP in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Using the U.K. Clinical Practice Research Datalink, we conducted a cohort study among 168,774 patients initiating antidiabetic drugs between January 2007 and March 2018. Using time-dependent Cox proportional hazards models, we estimated adjusted hazard ratios (HRs) with 95% CIs of incident BP associated with current use of DPP-4 inhibitors, compared with current use of other second- to third-line antidiabetic drugs. We also conducted a propensity score–matched analysis to assess the impact of residual confounding. RESULTS During 711,311 person-years of follow-up, 150 patients were newly diagnosed with BP (crude incidence rate, 21.1 per 100,000 person-years). Current use of DPP-4 inhibitors was associated with an increased risk of BP (47.3 vs. 20.0 per 100,000 person-years; HR 2.21 [95% CI 1.45–3.38]). HRs gradually increased with longer durations of use, reaching a peak after 20 months (HR 3.60 [95% CI 2.11–6.16]). Similar results were obtained in the propensity score–matched analysis (HR 2.40 [95% CI 1.13–4.66]). CONCLUSIONS In this large population-based study, use of DPP-4 inhibitors was associated with an at least doubling of the risk of BP in patients with type 2 diabetes, albeit the absolute risk was low.