Vildagliptin Significantly Increases the Risk of Bullous Pemphigoid: A Finnish Nationwide Registry Study

Varpuluoma, Outi; Försti, Anna-Kaisa; Jokelainen, Jari; Turpeinen, Miia; Timonen, Markku; Huilaja, Laura; Tasanen, Kaisa

doi:10.1016/j.jid.2018.01.027

Cited by 113 publications

(167 citation statements)

References 15 publications

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“…Likewise, a similar increase was also observed in a Japanese pharmacovigilance database, particularly among patients treated with vildagliptin, linagliptin, or teneligliptin (Arai, Shirakawa, Konishi, Sagawa, & Terauchi, 2018). Several observational studies (all case-control designs) have also been conducted and it was reported that a significantly increased or a trend towards an increased risk of BP is associated with the usage of DPP4is with odds ratios ranging between 1.58 and 3.16 (Benzaquen et al, 2018;Kridin & Bergman, 2018;Lee, Lee, Yoon, & Kim, 2019;Plaquevent, et al, 2019;Varpuluoma et al, 2018). Moreover, Benzaquen et al has reported that application of DPP4is increases the risk of BP of almost 3-fold, and the increase is associated with vildagliptin rather than other gliptins (Benzaquen et al, 2018).…”

Section: Dpp4/cd26 Inhibition and Bpsupporting

confidence: 60%

“…Increased risk in T2DM patients (Aouidad et al, 2013;Arai et al, 2018;Bene, et al, 2016;Benzaquen et al, 2018;Douros et al, 2019;Garcia et al, 2016;Kridin & Bergman, 2018;Lee et al, 2019;Plaquevent, et al, 2019;Varpuluoma et al, 2018) Taken together, these existing studies fail to strongly support the clinical application of DPP4is in either glucose control or β cell preservation in T1DM patients. The contrary conclusions obtained from the above clinic trials may be attributed to different baseline characteristics of the included patients (such as c-peptide levels, HbA1c, and disease duration), distinct follow-up lengths, different sample size, and other variables.…”

Section: Bpmentioning

confidence: 99%

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Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

Shao

et al. 2020

Pharmacology & Therapeutics

161

129

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Section: Dpp4/cd26 Inhibition and Bpsupporting

confidence: 60%

Section: Bpmentioning

confidence: 99%

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

Shao

et al. 2020

Pharmacology & Therapeutics

161

129

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“…Pharmacovigilance reports have reported mean latency periods ranging from 6 to 19 months. Varpuluoma and colleagues reported mean latency period between vildagliptin and BP onset of approximately 15 months. There are insufficient data to support whether BP is a drug‐induced adverse effect or whether DPPI brings out and exacerbates BP in those with underlying susceptibility.…”

Section: Discussionmentioning

confidence: 99%

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

2019

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Background/Objective There have been a number of case reports and small clinical series reporting the potential association between dipeptidyl peptidase‐4 inhibitors (DPPIs) for diabetes and the onset of bullous pemphigoid (BP). The aim of this study was to assess the association between DPPI use and BP, and whether this varied according to DPPI type. Methods We performed a systematic review and meta‐analysis according to PRISMA guidelines. We identified five studies with cases and controls. We performed unadjusted and adjusted meta‐analyses to assess the potential association. Results Adjusted meta‐analysis revealed significant association between DPPI use and BP (OR 2.13, 95% CI 1.59–2.86, I2 = 46%, P < 0.00001). This association was stronger between vildagliptin and BP (OR 5.08, 95% CI 1.70–15.19, P = 0.004) compared to linagliptin (OR 2.87, 95%CI 1.06–7.79, P = 0.04), and no association was found between sitagliptin and BP (OR 1.29, 95%CI 0.79–2.08, P = 0.31). Subgroup analysis demonstrated that the association between DPPI use and BP remained significant in males (OR 2.35, 95% CI 1.46–3.78, P = 0.0005) and females (OR 1.88, 95%CI 1.10–3.22, P = 0.02). Conclusions Limitations were that studies reviewed were retrospective by design which are susceptible to bias and lack of randomisation. Our adjusted analysis supports a significant association between DPPI use and onset of bullous pemphigoid. Vildagliptin had the highest odds of BP. These findings have clinical implications for dermatologists and the management of patients with diabetes and being treated with DPPI agents.

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“…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 .…”

Section: Discussionmentioning

confidence: 99%

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

Hung

Liu

Cheng

et al. 2019

The Journal of Dermatology

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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.

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Vildagliptin Significantly Increases the Risk of Bullous Pemphigoid: A Finnish Nationwide Registry Study

Cited by 113 publications

References 15 publications

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

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

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

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