Aims/hypothesis: Although benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been demonstrated in treatment of type 2 diabetes and weight management, their potential role in cancer prevention remains inadequately explored.

Methods: Using the TriNetX Research Network, we conducted a retrospective cohort study comparing new users of GLP-1RAs with users of other glucose-lowering medications. Propensity score matching was performed for demographic factors, socioeconomic factors, family history, lifestyle factors and cancer risk factors. The primary outcome was the incidence of obesity-related gastrointestinal cancers, and secondary outcomes were the incidence of individual cancer types.

Results: Using adjusted HRs (aHRs), GLP-1RA use was found to be associated with a significantly lower risk of overall gastrointestinal cancer compared with all other glucose-lowering medications (insulin: aHR 0.29; 95% CI 0.23, 0.37; metformin: aHR 0.84; 95% CI 0.71, 0.99; sulfonylureas: aHR 0.71; 95% CI 0.62, 0.80; thiazolidinediones: aHR 0.86; 95% CI 0.74, 0.99; dipeptidyl peptidase-4 inhibitors: aHR 0.80; 95% CI 0.70, 0.91; sodium-glucose cotransporter-2 inhibitors: aHR 0.80; 95% CI 0.68, 0.96). The protective effect was most pronounced compared with insulin therapy, with significant risk reductions across all individual cancers.

Conclusions/interpretation: GLP-1RA use is associated with a reduced risk of gastrointestinal cancers in individuals with type 2 diabetes. These findings suggest potential cancer-protective benefits of GLP-1RAs beyond their established roles in glycaemic management and weight reduction.

Keywords: Cancer; Colorectal cancer; Diabetes; Gastrointestinal; Glucagon-like peptide-1 receptor agonist; Insulin.

© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

目的/假设: 尽管胰高血糖素样肽-1受体激动剂（GLP-1RAs）在治疗2型糖尿病和体重管理方面的益处已被证实，但它们在癌症预防中的潜在作用尚未得到充分研究。

方法: 我们使用TriNetX Research Network进行了一项回顾性队列研究，比较了GLP-1RAs新使用者与其他降糖药物使用者的数据。根据人口统计学因素、社会经济因素、家族史、生活方式因素和癌症风险因素进行了倾向评分匹配。主要结局是肥胖相关胃肠癌的发病率，次要结局是个别癌症类型的发病率。

结果: 使用调整后的危险比（aHRs），GLP-1RA的使用与所有其他降糖药物相比整体胃肠癌的风险显著降低（胰岛素：aHR 0.29；95% CI 0.23，0.37；二甲双胍：aHR 0.84；95% CI 0.71，0.99；磺脲类药物：aHR 0.71；95% CI 0.62，0.80；噻唑烷二酮类药物：aHR 0.86；95% CI 0.74，0.99；二肽基肽酶-4抑制剂：aHR 0.80；95% CI 0.70，0.91；钠-葡萄糖共转运蛋白2抑制剂：aHR 0.80；95% CI 0.68，0.96）。与胰岛素治疗相比，保护作用最为明显，在所有个别癌症中均有显著的风险降低。

结论/解释: GLP-1RA的使用与2型糖尿病患者胃肠癌风险降低相关。这些发现表明，GLP-1RAs可能在血糖管理和体重减轻之外具有潜在的抗癌益处。

关键词: 癌症；结直肠癌；糖尿病；胃肠道；胰高血糖素样肽-1受体激动剂；胰岛素。