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Abstract
This case-control study examines the association between the use of dipeptidyl peptidase
4 inhibitors and the risk of developing bullous pemphigoid in patients with diabetes.
What is the association between use of dipeptidyl peptidase 4 inhibitors and the risk
of developing bullous pemphigoid in patients with diabetes? 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. Use of dipeptidyl peptidase 4 inhibitors, particularly
vildagliptin, may be associated with the development of bullous pemphigoid in male
patients with diabetes. 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. To characterize the potential association between the use of DPP-4 inhibitors
and an increased risk of developing BP. 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. 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. 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). 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.