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

Abstract

Recent studies revealed the risk of bullous pemphigoid (BP) in patients with diabetes mellitus (DM) taking dipeptidyl peptidase 4 (DPP‐4) inhibitors. To clarify the relationship between taking DPP‐4 inhibitors and the risk of BP among patients with DM, we conducted a cohort study by using the National Health Insurance Research Database of Taiwan from 1 January 2009 to 31 December 2015. We identified 6340 patients with DM taking DPP‐4 inhibitors and 25 360 DM patients who had not taken DPP‐4 inhibitors during the 7‐year follow‐up period. Compared with the non‐DPP‐4 inhibitor group, patients taking DDP‐4 inhibitors had a higher risk of BP (adjusted hazard ratio [aHR], 2.382; 95% confidence interval (CI), 1.163–4.883; P = 0.017]. Among the DPP‐4 inhibitors available in Taiwan, vildagliptin showed the highest risk of BP (aHR, 2.849; 95% CI, 1.893–4.215; P < 0.001), followed by saxagliptin (aHR, 2.657; 95% CI, 1.770–3.934; P < 0.001). Subgroup analysis revealed that the higher risk of BP was observed in patients older than 65 years (aHR, 2.403; 95% CI, 1.590–3.627; P < 0.001). This study revealed that treatment with DPP‐4 inhibitors, especially vildagliptin, was significantly associated with an increased risk of BP among DM patients.

The association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors: a ten-year prospective observational study

“…Since the introduction of DPP4-is as a standard treatment regimen for type 2 diabetes, numerous cases of patients developing BP following this treatment have been published [8,9]. In accordance with the results of our study, vildagliptin has shown the strongest correlation in most reports [2,10].…”

Bullous Pemphigoid: Trigger and Predisposing Factors

“…In that year, Pasmatzi and coworkers described two cases of BP induced by vildagliptin [ 25 ]. Moreover, one hundred cases of BP due to this DPP-4i, and to others, such as sitagliptin, linagliptin, saxagliptin, teneligliptin, anagliptin, and alogliptin, have been reported [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 34 , 35 , 36 , 37 , 38 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ] ( Table 1 ). Epidemiological evidence significantly supports the correlation of DPP-4i and BP onset.…”

“…The association between BP and radiotherapy has been widely described [ 68 , 108 , 109 , 110 ]. Hung and coworkers recently published a case-control study on female patients with autoimmune bullous diseases (BP and PV).…”

Dipeptidyl peptidase‐4 inhibitor‐related bullous pemphigoid: A comparative study of 100 patients with bullous pemphigoid and diabetes mellitus

“…15 Thereafter, an impressive body of epidemiological evidence confirming the association between DPP4i exposure and BP has emerged. [16][17][18][19] A recent meta-analysis has revealed that the exposure to DPP4i was associated with more than threefold increase risk of developing BP. 17 In general, it is often difficult to differentiate drug-induced BP from idiopathic BP (IBP), as they are clinically, histopathologically, and immunopathologically indistinguishable.…”