GLP-1 receptor agonists and pancreatic cancer risk: target trial emulation using real-world data

Lindsey Wang, QuanQiu Wang, Li Li, David C Kaelber, Rong Xu
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Abstract

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.
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GLP-1 受体激动剂与胰腺癌风险:利用真实世界数据模拟目标试验
背景有关胰高血糖素样肽-1 受体激动剂(GLP-1RA)对胰腺癌发病率影响的数据有限且不一致。在此,我们评估了在现实世界人群中,GLP-1RAs(单独使用或联合使用)与胰腺癌发病风险的关系,并根据肥胖和吸烟状况进行了分层。方法 该回顾性队列纳入了 2013 年 1 月至 2019 年 3 月期间处方 GLP-1RA 或其他非 GLP-1RA 抗糖尿病药物且既往未确诊胰腺癌的 T2DM 患者。对开具GLP-1RA与其他非GLP-1RA抗糖尿病药物的倾向分数匹配队列患者在5年随访期间的胰腺癌偶发(首次)诊断情况进行了比较。根据肥胖和烟草使用障碍状况对患者进行了分组分析。我们还比较了 GLP-1RA 联合疗法和单一疗法。采用 Cox 比例危险分析和 Kaplan-Meier 生存分析对首次发病时间进行了分析,并计算了危险比 (HR) 和 95% 置信区间 (CI)。结果 研究对象包括1,636,056名符合条件的患者,其中包括167,091名GLP-1RA处方患者和1,468,965名其他抗糖尿病药物处方患者。与六种非 GLP-1RA 抗糖尿病药物相比,GLP-1RA 可显著降低胰腺癌发病风险,HR 值介于 0.42 到 0.82 之间。有肥胖症和烟草使用障碍的患者比无肥胖症和烟草使用障碍的患者的发病风险降低幅度更大。与单一疗法相比,GLP-1RA 联合疗法可降低胰腺癌风险。结论 GLP-1RA 可降低 T2DM 患者的胰腺癌发病率。需要进一步的研究和试验来探索其机制并确认其因果效应。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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