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

Increased risk of bullous pemphigoid in dipeptidyl peptidase 4 inhibitors: A nationwide, population‐based, cohort study in Taiwan

“…The study also reported a strong association between vildagliptin and BP (OR, 5.08; 95% CI, 1.70–15.19; P = 0.004), followed by linagliptin (OR, 2.87; 95% CI, 1.06–7.79; P = 0.04), but not in sitagliptin (OR, 1.29; 95% CI, 0.79–2.08; P = 0.31). In Asia, a Korean retrospective, nationwide, case–control study of 670 case patients (DM and BP) and 670 control patients (DM only) showed that DPP‐4 inhibitors are associated with a significant risk of BP (adjusted odds ratio [aOR], 1.58; 95% CI, 1.25–2.00; P < 0.001) . The study further demonstrated that among all DPP‐4 inhibitors, vildagliptin was the most high risk of developing BP (aOR, 1.81; 95% CI, 1.31–2.50; P < 0.001).…”

“…The results of this large population‐based cohort study revealed that the use of DPP‐4 inhibitors was significantly related to an increased risk of BP with an aHR of 2.382 ( P = 0.017). The previous studies have elucidated the association between DPP‐4 inhibitors and BP . In 2019, a large population‐based cohort study of 8569 DPP‐4 inhibitor users and 160 205 non‐DPP‐4 inhibitor users was published by using the UK Clinical Practice Research Datalink .…”

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

“…Lee and colleagues performed a retrospective, nationwide case–control study using Korean insurance claims data from 2012 to 2016. Control cases with diabetes were randomly obtained from the same database after matching for age, gender and year of diagnosis.…”

Chronic prurigo: A retrospective study of 168 cases

“…There is little evidence that diabetes itself is involved in the development of Th2‐dominant PCM. However, antidiabetic agents, such a dipeptidyl peptidase‐4 inhibitor, increase the risk of development of bullous pemphigoid, a well‐known Th2‐dominant inflammatory skin condition . These observations therefore suggest the possibility of an association between PCM and diabetes.…”