Background Data on the effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on pancreatic cancer incidence are limited and inconsistent. Here we evaluate the association of GLP-1RAs, alone and in combinations, with incident pancreatic cancer risk in a real-world population, stratified by obesity and smoking status. Methods This retrospective cohort included patients with T2DM who were prescribed GLP-1RAs or other non-GLP-1RA anti-diabetes medications between January 2013 and March 2019 and had no prior diagnosis of pancreatic cancer. The incident (first-time) diagnosis of pancreatic cancer during a 5-year follow-up was compared between propensity-score matched cohorts of patients prescribed GLP-1RAs vs other non-GLP-1RA anti-diabetes medications. Subgroup analyses were performed in patients stratified by the status of obesity and tobacco use disorder. We also compared GLP-1RA combination therapies with monotherapies. Time-to-first-event analysis was performed using Cox proportional hazards and Kaplan-Meier survival analysis, with the hazard ratio (HR) and 95% confidence interval (CI) calculated. Results The study population comprised 1,636,056 eligible patients including 167,091 prescribed GLP-1RAs and 1,468,965 prescribed other anti-diabetes medications. GLP-1RAs were associated with a significantly decreased risk for pancreatic cancer incidence compared with each of six non-GLP-1RA anti-diabetes medications with HR ranging from 0.42 to 0.82. The reduction was greater in patients with obesity and tobacco use disorder than in those without. GLP-1RA combination therapies were associated with lower pancreatic cancer risk compared with monotherapies. Conclusions GLP-1RAs were associated with reduced pancreatic cancer incidence in patients with T2DM. Further studies and trials are needed to explore mechanisms and confirm causal effects.

中文翻译：

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GLP-1 受体激动剂和胰腺癌风险：使用真实世界数据的靶向试验模拟


背景 关于胰高血糖素样肽-1 受体激动剂 （GLP-1RAs） 对胰腺癌发病率影响的数据有限且不一致。在这里，我们评估了 GLP-1RAs（单独和联合使用）与真实世界人群中胰腺癌发病率风险的关联，按肥胖和吸烟状况分层。方法 该回顾性队列包括 2013 年 1 月至 2019年3月期间接受 GLP-1RAs 或其他非 GLP-1RA 抗糖尿病药物且既往未诊断为胰腺癌的 T2DM 患者。比较了 5 年随访期间胰腺癌的新 （首次） 诊断 在接受 GLP-1RAs 与其他非 GLP-1RA 抗糖尿病药物的患者队列的倾向评分匹配。对按肥胖和烟草使用障碍状况分层的患者进行亚组分析。我们还比较了 GLP-1RA 联合疗法与单药治疗。使用 Cox 比例风险和 Kaplan-Meier 生存分析进行首次事件时间分析，计算风险比 （HR） 和 95% 置信区间 （CI）。结果 研究人群包括 1,636,056 名符合条件的患者，包括 167,091 名处方 GLP-1RA 和 1,468,965 名处方其他抗糖尿病药物。与六种非 GLP-1RA 抗糖尿病药物相比，GLP-1RAs 与胰腺癌发病率风险显著降低相关，HR 范围为 0.42 至 0.82。肥胖和烟草使用障碍患者的减少幅度大于没有肥胖和烟草使用障碍的患者。与单一疗法相比，GLP-1RA 联合疗法与较低的胰腺癌风险相关。结论 GLP-1RAs 与 T2DM 患者胰腺癌发病率降低相关。 需要进一步的研究和试验来探索机制并确认因果效应。