Dipeptidyl peptidase-4 inhibitors and bullous pemphigoid: A systematic review and adjusted meta-analysis

Background/objective: There have been a number of case reports and small clinical series reporting the potential association between dipeptidyl peptidase-4 inhibitors (DPPIs) for diabetes and the onset of bullous pemphigoid (BP). The aim of this study was to assess the association between DPPI use and BP, and whether this varied according to DPPI type.

Methods: We performed a systematic review and meta-analysis according to PRISMA guidelines. We identified five studies with cases and controls. We performed unadjusted and adjusted meta-analyses to assess the potential association.

Results: Adjusted meta-analysis revealed significant association between DPPI use and BP (OR 2.13, 95% CI 1.59-2.86, I² = 46%, P < 0.00001). This association was stronger between vildagliptin and BP (OR 5.08, 95% CI 1.70-15.19, P = 0.004) compared to linagliptin (OR 2.87, 95%CI 1.06-7.79, P = 0.04), and no association was found between sitagliptin and BP (OR 1.29, 95%CI 0.79-2.08, P = 0.31). Subgroup analysis demonstrated that the association between DPPI use and BP remained significant in males (OR 2.35, 95% CI 1.46-3.78, P = 0.0005) and females (OR 1.88, 95%CI 1.10-3.22, P = 0.02).

Conclusions: Limitations were that studies reviewed were retrospective by design which are susceptible to bias and lack of randomisation. Our adjusted analysis supports a significant association between DPPI use and onset of bullous pemphigoid. Vildagliptin had the highest odds of BP. These findings have clinical implications for dermatologists and the management of patients with diabetes and being treated with DPPI agents.