Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
JAMA Dermatol. 2020 Oct 1;156(10):1107-1114. doi: 10.1001/jamadermatol.2020.2158.
Despite several recent reports on the elevated risk of bullous pemphigoid in patients with type 2 diabetes treated with dipeptidyl peptidase-4 (DPP-4) inhibitors, evidence on the absolute risk and comparative safety against other antidiabetics is limited.
To characterize the incidence rate of bullous pemphigoid associated with DPP-4 inhibitor use compared with second-generation sulfonylureas.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from 2 large commercial insurance claims databases (Optum Clinformatics Data Mart from October 17, 2006, to December 31, 2018, and IBM MarketScan Research Database from October 17, 2006, to December 31, 2017) and Medicare data from January 1, 2006, to December 31, 2016. Patients with type 2 diabetes who initiated treatment with DPP-4 inhibitors or second-generation sulfonylurea were included.
The primary outcome of the study was bullous pemphigoid, identified using diagnosis codes. After 1:1 propensity score matching, the incidence rates of bullous pemphigoid and the hazard ratios (HRs) with 95% CIs comparing patients who initiated DPP-4 inhibitor and second-generation sulfonylurea therapy were estimated. Subgroup analyses by age, sex, race, and individual DPP-4 agents were performed. The results from each database were pooled using inverse-variance fixed-effects meta-analysis.
A total of 1 664 880 patients who initiated DPP-4 inhibitors (51.0% female; mean [SD] age, 63.9 [9.7] years) and sulfonylurea (50.4% female; mean [SD] age, 63.9 [9.9] years) were included. The incidence rate of bullous pemphigoid per 1000 person-years was 0.42 in the DPP-4 inhibitor group vs 0.31 in the sulfonylurea group (HR, 1.42; 95% CI, 1.17-1.72). Higher rates per 1000 person-years for DPP-4 inhibitor vs sulfonylurea groups were seen in those who were 65 years or older (0.79 vs 0.49; HR, 1.62; 95% CI, 1.32-1.99), white (0.93 vs 0.54; HR, 1.70; 95% CI, 1.30-2.24), and treated with linagliptin (1.20 vs 0.55; HR, 1.68; 95% CI, 1.16-2.43).
This study found that patients who initiated DPP-4 inhibitor therapy had higher risk of bullous pemphigoid than those who initiated second-generation sulfonylurea therapy. Clinicians should be aware of this rare adverse effect of DPP-4 inhibitors in subgroups of patients who are older, white, and linagliptin users.
尽管最近有几项关于接受二肽基肽酶-4（DPP-4）抑制剂治疗的 2 型糖尿病患者发生大疱性类天疱疮风险升高的报告，但关于与其他抗糖尿病药物相比的绝对风险和相对安全性的证据有限。
描述与 DPP-4 抑制剂使用相关的大疱性类天疱疮的发病率，与第二代磺酰脲类药物进行比较。
设计、设置和参与者：这项队列研究使用了来自 2 个大型商业保险索赔数据库（Optum Clinformatics Data Mart，从 2006 年 10 月 17 日到 2018 年 12 月 31 日；以及 IBM MarketScan Research Database，从 2006 年 10 月 17 日到 2017 年 12 月 31 日）和 2006 年 1 月 1 日至 2016 年 12 月 31 日的医疗保险数据。纳入了开始接受 DPP-4 抑制剂或第二代磺酰脲类药物治疗的 2 型糖尿病患者。
本研究的主要结局是大疱性类天疱疮，通过诊断代码确定。在进行 1:1 倾向评分匹配后，估计了开始 DPP-4 抑制剂和第二代磺酰脲类药物治疗的患者中发生大疱性类天疱疮的发病率和 95%CI 的危害比（HR）。按年龄、性别、种族和个体 DPP-4 药物进行了亚组分析。使用逆方差固定效应荟萃分析汇总了来自每个数据库的结果。
共纳入了 1664880 名开始使用 DPP-4 抑制剂（51.0%为女性；平均[SD]年龄，63.9[9.7]岁）和磺酰脲类药物（50.4%为女性；平均[SD]年龄，63.9[9.9]岁）的患者。DPP-4 抑制剂组每 1000 人年的大疱性类天疱疮发病率为 0.42，磺酰脲组为 0.31（HR，1.42；95%CI，1.17-1.72）。在 65 岁或以上（0.79 比 0.49；HR，1.62；95%CI，1.32-1.99）、白人（0.93 比 0.54；HR，1.70；95%CI，1.30-2.24）和接受利拉利汀治疗的患者中（1.20 比 0.55；HR，1.68；95%CI，1.16-2.43），DPP-4 抑制剂组的发病率更高。
本研究发现，开始 DPP-4 抑制剂治疗的患者发生大疱性类天疱疮的风险高于开始第二代磺酰脲类药物治疗的患者。临床医生应注意到 DPP-4 抑制剂在年龄较大、为白人以及使用利拉利汀的患者亚组中出现这种罕见的不良反应。
