From the Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada.
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada.
Epidemiology. 2018 Nov;29(6):904-912. doi: 10.1097/EDE.0000000000000891.
Case reports have suggested a link between dipeptidyl peptidase-4 (DPP-4) inhibitors, antidiabetic drugs used as second- to third-line treatments, and incidence of rheumatoid arthritis. Because the DPP-4 enzyme is involved in several immunologic processes and possibly in the pathophysiology of rheumatoid arthritis, further research is warranted. This population-based study aimed to determine whether use of DPP-4 inhibitors is associated with incidence of rheumatoid arthritis.
Using the United Kingdom Clinical Practice Research Datalink, we conducted a cohort study among 144,603 patients with type 2 diabetes initiating antidiabetic drugs between 2007 and 2016. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for incident rheumatoid arthritis using time-dependent Cox proportional hazards models, comparing use of DPP-4 inhibitors with use of other antidiabetic drugs. We imposed a 6-month exposure lag period for latency and diagnostic delays. Secondary analyses included assessment of the duration-response relation and comparison with other second-line antidiabetic drugs, among others.
During 567,169 person-years of follow-up, 464 patients were newly diagnosed with rheumatoid arthritis (crude incidence rate: 82 per 100,000/year). Compared with use of other antidiabetic drugs, use of DPP-4 inhibitors was not associated with an increased risk of rheumatoid arthritis (82 vs. 79 per 100,000/year; HR = 1.0; 95% CI = 0.8, 1.3), with no evidence of duration-response relation. The results did not change after using second-line antidiabetic drugs as the comparator group.
In this large population-based study, use of DPP-4 inhibitors was not associated with an increased risk of incident rheumatoid arthritis.
病例报告表明，二肽基肽酶-4（DPP-4）抑制剂与作为二线至三线治疗药物的抗糖尿病药物之间存在关联，可导致类风湿关节炎的发病。由于 DPP-4 酶参与了多种免疫过程，并可能参与了类风湿关节炎的病理生理学过程，因此需要进一步的研究。本基于人群的研究旨在确定使用 DPP-4 抑制剂是否与类风湿关节炎的发病有关。
我们使用英国临床实践研究数据链，在 2007 年至 2016 年间，对 144603 例开始使用抗糖尿病药物的 2 型糖尿病患者进行了队列研究。我们使用时间依赖性 Cox 比例风险模型，比较了 DPP-4 抑制剂与其他抗糖尿病药物的使用情况，估算了类风湿关节炎发病的风险比（HR）及其 95%置信区间（CI）。我们为潜伏期和诊断延迟设定了 6 个月的暴露滞后期。次要分析包括评估与其他二线抗糖尿病药物的持续时间-反应关系的比较等。
在 567169 人年的随访期间，有 464 名患者新诊断为类风湿关节炎（粗发病率：82/100000 人/年）。与使用其他抗糖尿病药物相比，使用 DPP-4 抑制剂与类风湿关节炎的发病风险增加无关（82 与 79/100000 人/年；HR = 1.0；95%CI = 0.8, 1.3），且没有持续时间-反应关系的证据。在使用二线抗糖尿病药物作为比较组后，结果并未改变。
在这项大型基于人群的研究中，使用 DPP-4 抑制剂与新发类风湿关节炎的风险增加无关。
