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

Abstract Background Bullous pemphigoid is the most common bullous chronic autoimmune skin disease. Recent studies have suggested dipeptidyl-peptidase 4 inhibitors as possible predisposing agents of bullous pemphigoid. The objective of our study was to prospectively estimate the association between gliptins and the development of bullous pemphigoid. Methods We conducted a prospective study which included all patients diagnosed with biopsy-proven bullous pemphigoid in the Dermatology Department of our hospital between April 1, 2009 and December 31,2019. The diagnosis of bullous pemphigoid was based on specific clinical, histological and immunological features. Results Overall 113 consecutive patients (age 75 ± 13 years, 62 females) with the diagnosis of bullous pemphigoid were enrolled. Seventy-six patients (67.3%) suffered from type 2 Diabetes and 52 (46%) were treated with dipeptidyl-peptidase 4 inhibitors. The most frequent prescribed gliptin was vildagliptin, being administered to 45 cases (39.8% of total patients enrolled, 86.5% of the patients treated with gliptins). Gliptins were withdrawn immediately after the diagnosis of bullous pemphigoid, which together with steroid administration led to remission of the rash. Conclusions This study revealed that treatment with dipeptidyl-peptidase 4 inhibitors, especially vildagliptin, is significantly associated with an increased risk of bullous pemphigoid development.

Download Full-text

Association between dipeptidyl peptidase-4 inhibitors and risk of bullous pemphigoid in patients with diabetes: A population-based cohort study

10.21203/rs.3.rs-38822/v1 ◽

2020 ◽

Author(s):

Chen-Yi Wu ◽

Chun-Ying Wu ◽

Chung-Pin Li ◽

Yiing-Jenq Chou ◽

Yi-Hsian Lin ◽

...

Keyword(s):

Cohort Study ◽

Bullous Pemphigoid ◽

Cumulative Incidence ◽

Dipeptidyl Peptidase ◽

Diabetic Patients ◽

Diabetes Diagnosis ◽

Dipeptidyl Peptidase 4 ◽

Duration Of Diabetes ◽

Dipeptidyl Peptidase 4 Inhibitors ◽

Diabetes Patients

Abstract Background Higher bullous pemphigoid (BP) risk has been reported to be associated with dipeptidyl peptidase 4 inhibitor (DPP4i). However, large-scale studies to investigate the association between BP and DPP4i treatment are limited. The aim of this study is to examine the association between BP risk and DPP4i treatment in diabetes patients. Methods We conducted a nationwide cohort study based on the Taiwan National Health Insurance Database between 2000 and 2015. 124,619 diabetic patients who were receiving DPP4i therapy were matched 1: 1 with diabetic patients who had never received DPP4i by age, sex, duration of diabetes, insulin usage, and propensity score-matching of comorbidities. Results Of the 124,619 diabetes patients in the two groups, the mean age at diabetes diagnosis was 52.4 ± 10.9 years, with a mean duration of diabetes of 6.0 ± 3.9 years. After adjusting for competing mortality risk, the 6-year cumulative incidence of BP in the DPP4i-treated cohort was significantly higher than that in the non-DPP4i group (0.74 per 1000; 95% confidence interval [CI]: 0.51–1.05 vs 0.38 per 1000; 95% CI: 0.26–0.53, P = .001). The DPP4i and insulin-treated group had the highest 6-year cumulative incidence for BP (0.93; 95% CI: 0.54–1.54 per 1000). Modified Cox regression analysis revealed that DPP4i treatment (HR: 2.15, 95% CI: 1.18–3.91, P = 0.01), age (HR: 1.06, P < .001), renal disease (HR: 2.32, P < .001), and metformin user (HR: 1.93, P = 0.006) were associated with increased BP risk. Conclusion DPP4i users had a 2.2-fold increase in the risk of BP, and the risk was the highest in those with concomitant use of DPP4i and insulin. The use of DPP4is as anti-diabetic medications must be monitored carefully and may be replaced by other anti-diabetic medications in BP patients.

Download Full-text

Dipeptidyl peptidase‐4 inhibitors lower the risk of autoimmune disease in patients with type 2 diabetes mellitus: A nationwide population‐based cohort study

British Journal of Clinical Pharmacology ◽

10.1111/bcp.13955 ◽

2019 ◽

Vol 85 (8) ◽

pp. 1719-1727 ◽

Cited By ~ 12

Author(s):

Jong‐Mi Seong ◽

Jeong Yee ◽

Hye Sun Gwak

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Cohort Study ◽

Autoimmune Disease ◽

Dipeptidyl Peptidase ◽

Population Based ◽

Dipeptidyl Peptidase 4 ◽

Dipeptidyl Peptidase 4 Inhibitors

Download Full-text

Dipeptidyl peptidase-4 inhibitors and incidence of inflammatory bowel disease among patients with type 2 diabetes: population based cohort study

BMJ ◽

10.1136/bmj.k872 ◽

2018 ◽

pp. k872 ◽

Cited By ~ 45

Author(s):

Devin Abrahami ◽

Antonios Douros ◽

Hui Yin ◽

Oriana Hoi Yun Yu ◽

Christel Renoux ◽

...

Keyword(s):

Type 2 Diabetes ◽

Inflammatory Bowel Disease ◽

Cohort Study ◽

Bowel Disease ◽

Dipeptidyl Peptidase ◽

Population Based ◽

Dipeptidyl Peptidase 4 ◽

Dipeptidyl Peptidase 4 Inhibitors ◽

Inflammatory Bowel

Download Full-text

Dipeptidyl Peptidase-4 Inhibitors and the Risk of Pancreatitis in Patients with Type 2 Diabetes Mellitus: A Population-Based Cohort Study

Journal of Diabetes Research ◽

10.1155/2018/5246976 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Young-Gun Kim ◽

Seirhan Kim ◽

Seung Jin Han ◽

Dae Jung Kim ◽

Kwan-Woo Lee ◽

...

Keyword(s):

Acute Pancreatitis ◽

Cohort Study ◽

Proportional Hazards ◽

National Sample ◽

Dipeptidyl Peptidase ◽

Population Based ◽

Cox Proportional Hazards ◽

Drug Induced ◽

Dipeptidyl Peptidase 4 ◽

Dipeptidyl Peptidase 4 Inhibitors

Background. Information on the risk of acute pancreatitis in patients receiving dipeptidyl-peptidase IV inhibitors (DPP-4i) is limited and controversial. One study suggested that the differences in findings between these meta-analyses were attributed to whether they included large randomized control trials with cardiovascular outcomes or not. The aim of our study was to determine whether the use of DPP-4i increases the risk of acute pancreatitis compared with sulfonylurea (SU) and whether the risk is higher in patients with underlying cardiovascular disease (CVD). Methods. A population-based cohort study was performed using Korean National Health Insurance Service-National Sample Cohort data. We included 33,395 new users of SU and DPP-4i from 1 January 2008 to 31 December 2015. SU-treated patients and DPP-4i-treated patients were matched by 1 : 1 propensity score matching. We used Kaplan–Meier curves and Cox proportional hazards regression analysis to calculate the risk of acute pancreatitis. Results. The hazard ratio (HR) of hospitalization for acute pancreatitis was 0.642 (95% confidence interval (CI): 0.535–0.771) in DPP-4i-treated patients compared with SU-treated patients. The HR of DPP-4i use was also lower than that of SU use in patients without underlying CVD (HR: 0.591; 95% CI: 0.476–0.735) but not in patients with underlying CVD (HR: 0.727; 95% CI: 0.527–1.003). Conclusion. Our findings suggest that DPP-4i is less likely to cause drug-induced pancreatitis than SU. This finding was not evident in patients with CVD, but DPP-4i was not more likely to induce pancreatitis in these patients than SU was.

Download Full-text