Objective 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.
Design Population based cohort study.
Setting More than 700 general practices contributing data to the United Kingdom Clinical Practice Research Datalink.
Participants 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.
Main outcome measures 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.
Results 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 v 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.
Conclusions 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.

目的评估二肽基肽酶-4抑制剂的使用是否与2型糖尿病患者炎症性肠病的发生有关。
设计基于人群的队列研究。
设置700多种常规做法，为英国临床实践研究数据链接提供数据。
参与者141170名患者（年龄至少18岁）于2007年1月1日至2016年12月31日期间开始使用抗糖尿病药物，并随访至2017年6月30日。
主要结局指标使用累积的持续时间和使用开始后的时间，对与使用二肽基肽酶-4抑制剂相关的事件性炎症性肠病的调整后的危险比，使用时间依赖性Cox比例危害模型进行估算。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的使用进行比较，暴露时间滞后六个月以解决潜伏期和诊断延迟。
结果在552 413人年的随访期间，发生了208起炎症性肠病事件（每10万人年的粗发病率为37.7（95％置信区间32.7至43.1））。总体而言，使用二肽基肽酶-4抑制剂会增加炎症性肠病的风险（53.4 v每10万人年34.5；危险比1.75，95％置信区间1.22至2.49）。危险比随着使用时间的延长而逐渐增加，在使用三到四年后达到峰值（危险比2.90，从1.31到6.41），在使用四年以上后降低（1.45，从0.44到4.76）。自从开始使用二肽基肽酶-4抑制剂以来，随着时间的推移，观察到了类似的模式。这些发现在一些敏感性分析中保持一致。
结论在第一项基于人群的研究中，使用二肽基肽酶4抑制剂与炎症性肠病的风险增加相关。尽管这些发现需要重复，但医生应意识到这种可能的关联。