Incretin-based Drugs and the Incidence of Colorectal Cancer in Patients with Type 2 Diabetes
Incretin-based Drugs and the Incidence of Colorectal Cancer in Patients with Type 2 Diabetes
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DOI：
10.1097/ede.0000000000000793
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发表时间：
2018-03-01
期刊：
影响因子：
5.4
通讯作者：
Azoulay, Laurent
中科院分区：
文献类型：
--
作者：
Abrahami, Devin;Yin, Hui;Azoulay, Laurent
背景资料：肠促胰岛素类药物（胰高血糖素样肽-1 [GLP-1]类似物和二肽基肽酶-4 [DPP-4]抑制剂）治疗结直肠癌的安全性证据相互矛盾。本研究的目的是确定是否使用肠促胰岛素为基础的药物与2型diabetes.Methods患者发生结直肠癌的风险相关：使用英国临床实践研究Datalink的数据，我们确定了一个队列的112,040例新治疗的抗糖尿病药物之间的2007年1月1日和2015年3月31日。我们将GLP-1类似物和DPP-4抑制剂的使用作为时变变量进行建模，并将其与磺脲类药物的使用进行比较。我们将暴露延迟1年，以减少反向因果关系和检测偏倚。我们使用时间依赖性考克斯比例风险模型，通过累积使用时间和开始使用时间，估计与GLP-1类似物和DPP-4抑制剂使用相关的结肠直肠癌事件的风险比（95%置信区间）。（发病率：1.9/1000人-年）。GLP-1类似物的使用与结直肠癌发病率无关（风险比：1.0; 95%置信区间= 0.7，1.6），DPP-4抑制剂的使用也与结直肠癌发病率无关（风险比：1.2; 95%置信区间= 1.0，1.5）。没有证据表明，持续时间的反应关系为任一drug.Conclusions：这个大规模的人口为基础的研究结果表明，使用肠促胰岛素为基础的药物与2型糖尿病患者的结直肠癌的发病率。
Background: Evidence on the safety of the incretin-based drugs (glucagon-like peptide-1 [GLP-1] analogues and dipeptidyl peptidase-4 [DPP-4] inhibitors) with respect to colorectal cancer is contradictory. The objective of this study was to determine whether use of incretin-based drugs is associated with risk of incident colorectal cancer in patients with type 2 diabetes.Methods: Using data from the UK Clinical Practice Research Datalink, we identified a cohort of 112,040 patients newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2015. We modeled use of GLP-1 analogues and DPP-4 inhibitors as time-varying variables and compared them with use of sulfonylureas. We lagged exposures by 1 year for latency and to reduce reverse causality and detection bias. We used time-dependent Cox proportional hazards models to estimate hazard ratios with 95% confidence intervals of incident colorectal cancer associated with the use of GLP-1 analogues and DPP-4 inhibitors overall, by cumulative duration of use and by time since initiation.Results: During 388,619 person-years of follow-up, there were 733 incident colorectal cancer events (incidence rate: 1.9 per 1,000 person-years). Use of GLP-1 analogues was not associated with colorectal cancer incidence (hazard ratio: 1.0; 95% confidence interval = 0.7, 1.6), nor was use of DPP-4 inhibitors (hazard ratio: 1.2; 95% confidence interval = 1.0, 1.5). There was no evidence of a duration-response relation for either drug.Conclusions: The results of this large population-based study indicate that use of incretin-based drugs is not associated with colorectal cancer incidence among patients with type 2 diabetes.