From the Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada.
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.
Epidemiology. 2022 Jul 1;33(4):563-571. doi: 10.1097/EDE.0000000000001486. Epub 2022 Mar 29.
There is some evidence that glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors have chemopreventive effects on prostate cancer cells but real-world evidence for this possible effect is lacking. Thus, the objective of this study was to estimate whether use of GLP-1 receptor agonists and DPP-4 inhibitors, separately, is associated with a decreased risk of prostate cancer among patients with type 2 diabetes.
We assembled two new-user, active-comparator cohorts using the UK Clinical Practice Research Datalink (2007 to 2019). The first cohort included 5,063 initiators of GLP-1 receptor agonists and 112,955 of sulfonylureas. The second cohort included 53,529 initiators of DPP-4 inhibitors and 114,417 of sulfonylureas. We fit Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer. We weighted the models using propensity score fine stratification, which considered over 50 potential confounders.
GLP-1 receptor agonists were associated with a decreased risk of prostate cancer when compared with sulfonylureas (incidence rates = 156.4 vs. 232.0 per 100,000 person-years, respectively; HR = 0.65; 95% CI = 0.43, 0.99). DPP-4 inhibitors were also associated with a decreased risk of prostate cancer when compared with sulfonylureas (incidence rates = 316.2 vs. 350.5 events per 100,000 person-years, respectively; HR = 0.90; 95% CI = 0.81, 1.00).
The results of this study are consistent with the hypothesis that the use of GLP-1 receptor agonists and DPP-4 inhibitors, separately, may decrease the risk of prostate cancer when compared with the use of sulfonylureas.
有一些证据表明，胰高血糖素样肽 1（GLP-1）受体激动剂和二肽基肽酶-4（DPP-4）抑制剂对前列腺癌细胞具有化学预防作用，但缺乏这种可能效果的真实世界证据。因此，本研究的目的是评估单独使用 GLP-1 受体激动剂和 DPP-4 抑制剂是否与 2 型糖尿病患者的前列腺癌风险降低相关。
我们使用英国临床实践研究数据链接（2007 年至 2019 年）组建了两个新用户、活性对照队列。第一个队列包括 5063 名 GLP-1 受体激动剂和 112955 名磺酰脲类药物的起始者。第二个队列包括 53529 名 DPP-4 抑制剂和 114417 名磺酰脲类药物的起始者。我们使用 Cox 比例风险模型估计前列腺癌的调整后的风险比（HR）和 95%置信区间（CI）。我们使用倾向评分精细分层对模型进行加权，该分层考虑了 50 多个潜在混杂因素。
与磺酰脲类药物相比，GLP-1 受体激动剂与前列腺癌风险降低相关（发生率分别为 156.4 和 232.0 例/100000 人年；HR=0.65；95%CI=0.43，0.99）。与磺酰脲类药物相比，DPP-4 抑制剂也与前列腺癌风险降低相关（发生率分别为 316.2 和 350.5 例/100000 人年；HR=0.90；95%CI=0.81，1.00）。
本研究结果与假设一致，即与使用磺酰脲类药物相比，单独使用 GLP-1 受体激动剂和 DPP-4 抑制剂可能会降低前列腺癌的风险。
