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Original Investigation
January 9, 2019

Association of Dipeptidyl Peptidase 4 Inhibitor Use With Risk of Bullous Pemphigoid in Patients With Diabetes

Author Affiliations
  • 1Department of Dermatology, Bundang CHA Medical Center, CHA University School of Medicine, Seongnam, Republic of Korea
JAMA Dermatol. Published online January 9, 2019. doi:10.1001/jamadermatol.2018.4556
Key Points

Questions  What is the association between use of dipeptidyl peptidase 4 inhibitors and the risk of developing bullous pemphigoid in patients with diabetes?

Findings  In this population-based, case-control study of insurance claims data from 1340 patients in Korea, the proportion of patients with diabetes among all patients with bullous pemphigoid increased between 2012 and 2016 and use of dipeptidyl peptidase 4 inhibitors was significantly associated with an increased risk of developing bullous pemphigoid in patients with diabetes compared with control patients. The risk of bullous pemphigoid was highest in male patients using vildagliptin.

Meaning  Use of dipeptidyl peptidase 4 inhibitors, particularly vildagliptin, may be associated with the development of bullous pemphigoid in male patients with diabetes.

Abstract

Importance  Recent studies suggest that dipeptidyl peptidase 4 (DPP-4) inhibitors are associated with an increased risk of developing bullous pemphigoid (BP). Population-based studies on the association between DPP-4 inhibitors and BP are limited.

Objective  To characterize the potential association between the use of DPP-4 inhibitors and an increased risk of developing BP.

Design, Setting, and Participants  This retrospective, nationwide, population-based, case-control study using Korean insurance claims data from January 1, 2012, to December 31, 2016, included patients with newly diagnosed BP and diabetes. Control patients with diabetes (and without BP) were randomly obtained after matching for age, sex, and year of diagnosis within the same period.

Main Outcomes and Measures  The number of patients with newly diagnosed BP and diabetes per year and annual changes in the proportion of patients with diabetes among all patients with BP were measured. The association between use of DPP-4 inhibitors and risk of developing BP was analyzed using univariate and multivariate logistic regression analyses.

Results  The study included 670 case patients (with diabetes and BP) and 670 control patients (with only diabetes) (mean [SD] age, 75.3 [10.0] years in each group; 342 [51.0%] male in each group). The number of patients with diabetes and BP more than doubled during the study period (from 77 in 2012 to 206 in 2016). The proportion of patients with diabetes among all patients with BP also increased (from 0.18 in 2012 to 0.33 in 2016). The use of DPP-4 inhibitors was associated with a significant increase in the risk of developing BP (adjusted odds ratio [aOR], 1.58; 95% CI, 1.25-2.00; P < .001); among all DPP-4 inhibitors used in Korea, the highest aOR was associated with the use of vildagliptin (aOR, 1.81; 95% CI, 1.31-2.50; P < .001). Subgroup analyses revealed a significant association in male patients (aOR, 1.91; 95% CI, 1.39-2.63; P < .001) and that vildagliptin was the most high-risk DPP-4 inhibitor (aOR, 2.70; 95% CI, 1.73-4.34; P < .001).

Conclusions and Relevance  The findings suggest that DPP-4 inhibitors are associated with a significantly increased risk of the development of BP in patients with diabetes. Of the DPP-4 inhibitors available in Korea, vildagliptin was associated with the highest risk, particularly in male patients. Practitioners should consider that DPP-4 inhibitors, particularly vildagliptin, may be associated with the development of BP in patients with diabetes. These nationwide, population-based results may serve as a foundation for further studies seeking to understand how DPP-4 inhibitors contribute to the development of BP.

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