Department of Health Care Administration and Management, Graduate School of Medical Sciences, Kyushu University, Fukuoka City, Fukuoka, Japan.
Department of General Internal Medicine, Local Incorporated Administrative Agency Saga-Ken Medical Centre Koseikan, Saga, Japan.
J Diabetes Investig. 2023 Jun;14(6):756-766. doi: 10.1111/jdi.14004. Epub 2023 Mar 10.
AIMS/INTRODUCTION: Although the association between dipeptidyl peptidase-4 (DPP-4) inhibitors and bullous pemphigoid (BP) has begun to be established, some studies have suggested there are risk differences among DPP-4 inhibitors. We conducted a population-based cohort study to examine the risk differences.
Using the claims databases of the Fukuoka Prefecture Wide-Area Association of Latter-Stage Elderly Healthcare between April 1, 2013 and March 31, 2017, we conducted a retrospective cohort study to compare patients receiving one DPP-4 inhibitor with those who were prescribed another antidiabetic drug. The primary outcome was an adjusted hazard ratio (HR) of the development of bullous pemphigoid during a 3-year follow-up. The secondary outcome was the development of BP requiring systemic steroids immediately after the diagnosis. These were estimated using Cox proportional hazards regression models.
The study comprised 33,241 patients, of which 0.26% (n = 88) developed bullous pemphigoid during follow-up. The percentages of patients with bullous pemphigoid who required immediate systemic steroid treatment was 0.11% (n = 37). We analyzed four DPP-4 inhibitors: sitagliptin, vildagliptin, alogliptin, and linagliptin. Vildagliptin and linagliptin raised the risk of BP significantly (primary outcome, vildagliptin, HR 2.411 [95% confidence interval (CI) 1.325-4.387], linagliptin, HR 2.550 [95% CI 1.266-5.136], secondary outcome, vildagliptin HR 3.616 [95% CI 1.495-8.745], linagliptin HR 3.556 [95% CI 1.262-10.024]). A statistically significant risk elevation was not observed with sitagliptin and alogliptin (primary outcome, sitagliptin, HR 0.911 [95% CI 0.508-1.635], alogliptin, HR 1.600 [95% CI 0.714-3.584], secondary outcome, sitagliptin, HR 1.192 [95% CI 0.475-2.992], alogliptin, HR 2.007 [95% CI 0.571-7.053]).
Not all the DPP-4 inhibitors could induce bullous pemphigoid significantly. Therefore, the association warrants further investigations before generalization.
目的/引言：虽然二肽基肽酶-4（DPP-4）抑制剂与大疱性类天疱疮（BP）之间的关联已开始确立，但一些研究表明 DPP-4 抑制剂之间存在风险差异。我们进行了一项基于人群的队列研究，以检查风险差异。
我们使用福冈县后期老年人医疗保健广域协会的理赔数据库，对 2013 年 4 月 1 日至 2017 年 3 月 31 日期间的患者进行回顾性队列研究，比较接受一种 DPP-4 抑制剂的患者与接受另一种抗糖尿病药物的患者。主要结局是在 3 年随访期间发生大疱性类天疱疮的调整后的危险比（HR）。次要结局是在诊断后立即需要全身类固醇治疗的 BP 发生情况。这些通过 Cox 比例风险回归模型进行估计。
研究共纳入 33241 名患者，其中 0.26%（n=88）在随访期间发生大疱性类天疱疮。需要立即进行全身类固醇治疗的大疱性类天疱疮患者比例为 0.11%（n=37）。我们分析了四种 DPP-4 抑制剂：西他列汀、维格列汀、阿格列汀和利格列汀。维格列汀和利格列汀显著增加了 BP 的风险（主要结局，维格列汀，HR 2.411[95%置信区间（CI）1.325-4.387]，利格列汀，HR 2.550[95%CI 1.266-5.136]），次要结局，维格列汀 HR 3.616[95%CI 1.495-8.745]，利格列汀 HR 3.556[95%CI 1.262-10.024]）。西他列汀和阿格列汀未观察到统计学意义上的风险升高（主要结局，西他列汀，HR 0.911[95%CI 0.508-1.635]，阿格列汀，HR 1.600[95%CI 0.714-3.584]，次要结局，西他列汀，HR 1.192[95%CI 0.475-2.992]，阿格列汀，HR 2.007[95%CI 0.571-7.053]）。
并非所有 DPP-4 抑制剂都会显著诱导大疱性类天疱疮。因此，在推广之前，需要进一步调查这种关联。
