Regardless of the diagnosis of type 2 diabetes, patients with bullous pemphigoid who take dipeptidyl peptidase-4 inhibitors (DPP4Is) test positive for anti-BP180NC16a antibody less often than those who do not take DPP4Is, according to a study published in the Journal of Diabetes Investigation.

It is widely believed that bullous pemphigoid is a drug-induced condition. To evaluate the relationship between bullous pemphigoid and DDP4Is, researchers conducted a retrospective study of data from 168 adults (average age 79.7 years) diagnosed with bullous pemphigoid.

Researchers determined that 48 participants had type 2 diabetes, and DPP4Is were prescribed to 32 participants, 65.6% of whom tested positive for anti-BP180NC16a antibody. Meanwhile, 82.3% of participants who did not receive DPP4Is tested positive for the antibody. 

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Furthermore, 16 patients with type 2 diabetes had not been prescribed a DPP4I, and only one of these patients tested positive for the antibody. Throughout the study period, 9304 patients were prescribed DPP4Is, and bullous pemphigoid developed in 8. Of those, 6 had a non-inflammatory form, and tests were negative for the antibody in 5. Despite its slightly reduced prevalence rate, researchers continue to warn of the risk of using DPP4I for diabetes treatment.

Among patients who used DPP4Is prior to bullous pemphigoid onset, researchers also analyzed antibody titers. The titer was found to be low in both the overall population and in those with type 2 diabetes.

Several limitations were noted for this study. Most notably, because many patients who were prescribed DPP4Is were transferred to other hospitals, the researchers were unable to determine the incidence of bullous pemphigoid for the entire initial population accurately.

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Taking into account such limitations, researchers said of their findings, “We consider that it is highly important to identify the features of DPP4I-induced bullous pemphigoid. Although DPP4Is are effective drugs for the treatment of diabetes, care should be taken regarding the development of bullous pemphigoid.”


Kawaguchi Y, Shimauchi R, Nishibori N et al. Dipeptidyl peptidase-4 inhibitors-associated bullous pemphigoid: a retrospective study of 168 pemphigoid and 9,304 diabetes mellitus cases [published online June 19, 2018]. J Diabetes Investig. doi: 10.1111/jdi.12877