Abrahami Devin, Douros Antonios, Yin Hui, Yu Oriana Hoi Yun, Renoux Christel, Bitton Alain, Azoulay Laurent
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada H3T 1E2.
Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada.
BMJ. 2018 Mar 21;360:k872. doi: 10.1136/bmj.k872.
To assess whether the use of dipeptidyl peptidase-4 inhibitors is associated with the incidence of inflammatory bowel disease in patients with type 2 diabetes.
Population based cohort study.
More than 700 general practices contributing data to the United Kingdom Clinical Practice Research Datalink.
A cohort of 141 170 patients, at least 18 years of age, starting antidiabetic drugs between 1 January 2007 and 31 December 2016, with follow-up until 30 June 2017.
Adjusted hazard ratios for incident inflammatory bowel disease associated with use of dipeptidyl peptidase-4 inhibitors overall, by cumulative duration of use, and by time since initiation, estimated using time dependent Cox proportional hazards models. Use of dipeptidyl peptidase-4 inhibitors was modelled as a time varying variable and compared with use of other antidiabetic drugs, with exposures lagged by six months to account for latency and diagnostic delays.
During 552 413 person years of follow-up, 208 incident inflammatory bowel disease events occurred (crude incidence rate of 37.7 (95% confidence interval 32.7 to 43.1) per 100 000 person years). Overall, use of dipeptidyl peptidase-4 inhibitors was associated with an increased risk of inflammatory bowel disease (53.4 34.5 per 100 000 person years; hazard ratio 1.75, 95% confidence interval 1.22 to 2.49). Hazard ratios gradually increased with longer durations of use, reaching a peak after three to four years of use (hazard ratio 2.90, 1.31 to 6.41) and decreasing after more than four years of use (1.45, 0.44 to 4.76). A similar pattern was observed with time since starting dipeptidyl peptidase-4 inhibitors. These findings remained consistent in several sensitivity analyses.
In this first population based study, the use of dipeptidyl peptidase-4 inhibitors was associated with an increased risk of inflammatory bowel disease. Although these findings need to be replicated, physicians should be aware of this possible association.
评估2型糖尿病患者使用二肽基肽酶-4抑制剂是否与炎症性肠病的发病率相关。
基于人群的队列研究。
700多家全科诊所向英国临床实践研究数据链提供数据。
141170名年龄至少18岁的患者队列，于2007年1月1日至2016年12月31日开始使用抗糖尿病药物，随访至2017年6月30日。
使用时间依赖的Cox比例风险模型估计与总体使用二肽基肽酶-4抑制剂、使用累积持续时间以及开始使用后的时间相关的炎症性肠病发病的调整风险比。将二肽基肽酶-4抑制剂的使用建模为随时间变化的变量，并与其他抗糖尿病药物的使用进行比较，暴露滞后6个月以考虑潜伏期和诊断延迟。
在552413人年的随访期间，发生了208例炎症性肠病事件（粗发病率为每100000人年37.7例（95%置信区间32.7至43.1））。总体而言，使用二肽基肽酶-4抑制剂与炎症性肠病风险增加相关（每100000人年53.4例对34.5例；风险比1.75，95%置信区间1.22至2.49）。风险比随着使用持续时间的延长而逐渐增加，在使用三到四年后达到峰值（风险比2.90，1.31至6.41），在使用超过四年后下降（1.45，0.44至4.76）。自开始使用二肽基肽酶-4抑制剂后的时间也观察到类似模式。这些发现在多项敏感性分析中保持一致。
在这项首次基于人群的研究中，使用二肽基肽酶-4抑制剂与炎症性肠病风险增加相关。尽管这些发现需要重复验证，但医生应意识到这种可能的关联。
