Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, 3755 Côte Sainte-Catherine, H-425.1, Montréal H3T 1E2, Canada.
Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal.
BMJ. 2016 Oct 20;355:i5340. doi: 10.1136/bmj.i5340.
To determine whether the use of glucagon-like peptide-1 (GLP-1) analogues, compared with the use of dipeptidylpeptidase-4 (DPP-4) inhibitors, is associated with an increased risk of incident breast cancer in patients with type 2 diabetes.
Population based cohort study.
Clinical Practice Research Datalink, UK.
44 984 women aged at least 40 years, who were newly treated with glucose lowering drugs between 1 January 2007 and 31 March 2015, with follow-up until 31 March 2016.
Time varying use of GLP-1 analogues compared with use of DPP-4 inhibitors, with exposures lagged by one year for latency purposes. Time dependent Cox proportional hazards models were used to estimate adjusted hazard ratios with 95% confidence intervals of incident breast cancer associated with use of GLP-1 analogues overall, by cumulative duration of use, and time since initiation.
The cohort was followed for a mean of 3.5 years (standard deviation 2.2), with 549 incident events of breast cancer recorded (crude incidence 3.5 (95% confidence interval 3.3 to 3.8) per 1000 person years). Overall, compared with use of DPP-4 inhibitors, use of GLP-1 analogues was not associated with an increased risk of breast cancer (incidence 4.4 v 3.4 per 1000 person years; hazard ratio 1.40 (95% confidence interval 0.91 to 2.16)). Hazard ratios gradually increased with longer durations of use, with a peak between two to three years of GLP-1 use (2.66 (95% confidence interval 1.32 to 5.38)), and returned closer to the null after more than three years of use (0.98 (0.24 to 4.03)). A similar pattern was observed with time since initiation of GLP-1 analogues.
In this population based cohort study, use of GLP-1 analogues was not associated with an overall increased risk of breast cancer. Although it is not possible to rule out a tumour promoter effect, the observed duration-response associations are likely the result of a transient increase in detection of breast cancers in GLP-1 analogue users.
确定与二肽基肽酶-4（DPP-4）抑制剂相比，使用胰高血糖素样肽-1（GLP-1）类似物是否与 2 型糖尿病患者乳腺癌发病风险增加相关。
基于人群的队列研究。
英国临床实践研究数据链。
44984 名年龄至少 40 岁的女性，她们在 2007 年 1 月 1 日至 2015 年 3 月 31 日期间开始接受降血糖药物治疗，随访至 2016 年 3 月 31 日。
GLP-1 类似物的时间变化使用与 DPP-4 抑制剂的使用进行比较，潜伏期目的为暴露滞后一年。使用时间依赖性 Cox 比例风险模型估计 GLP-1 类似物使用与总体乳腺癌发病相关的调整后的危险比及其 95%置信区间，按累积使用时间和起始时间进行分层。
该队列的平均随访时间为 3.5 年（标准差为 2.2），共记录到 549 例乳腺癌事件（粗发病率为 3.5（95%置信区间为 3.3 至 3.8）/1000 人年）。总体而言，与使用 DPP-4 抑制剂相比，使用 GLP-1 类似物与乳腺癌发病风险增加无关（发病率分别为 4.4 与 3.4/1000 人年；危险比为 1.40（95%置信区间为 0.91 至 2.16））。随着使用时间的延长，风险比逐渐升高，在使用 GLP-1 约 2 至 3 年时达到峰值（2.66（95%置信区间为 1.32 至 5.38）），使用超过 3 年后接近零（0.98（95%置信区间为 0.24 至 4.03））。从 GLP-1 类似物起始时间开始，也观察到类似的模式。
在这项基于人群的队列研究中，使用 GLP-1 类似物与乳腺癌发病风险总体增加无关。虽然不能排除促肿瘤效应，但观察到的时间-反应关联可能是 GLP-1 类似物使用者中乳腺癌检测暂时增加的结果。
