Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated significant efficacy in obesity treatment beyond their original development for type-2 diabetes management. This comprehensive study investigated the relationship between GLP-1RA use and cancer incidence in individuals with obesity across a 5-year follow-up period.Methods: We conducted a large-scale cohort study using the TriNetX US Collaborative Network database (2013–2023) examining adult patients with obesity. The study utilized propensity score matching to pair GLP-1RA-treated patients with controls (1:1) using the nearest neighbor method. Cancer incidence served as the primary outcome measure over the 5-year follow-up, with subgroup analyses considering individual GLP-1RA agents, patient sex, and BMI categories.Results: Analysis revealed significant cancer-risk reductions associated with GLP-1RA use across multiple cancer types compared to matched controls. Notable risk reductions were observed in gastrointestinal (HR 0.67, 95% CI 0.59–0.75), skin (HR 0.62, 95% CI 0.55–0.70), breast (HR 0.72, 95% CI 0.64–0.82), female genital (HR 0.61, 95% CI 0.53–0.71), prostate (HR 0.68, 95% CI 0.58–0.80), and lymphoid/hematopoietic cancers (HR 0.69, 95% CI 0.60–0.80). Semaglutide demonstrated superior protective effects, particularly in gastrointestinal cancers (HR 0.45, 95% CI 0.37–0.53). Conversely, liraglutide showed increased risks for thyroid (HR 1.70, 95% CI 1.03–2.82) and respiratory cancers (HR 1.62, 95% CI 1.13–2.32).Conclusions: This research provides compelling evidence for GLP-1RA’s potential role in cancer-risk reduction, with semaglutide showing particularly promising results. The differential effects observed among GLP-1RA agents emphasize the importance of personalized medicine approaches. These findings suggest significant implications for clinical practice and future research in both obesity management and cancer prevention.
背景：胰高血糖素样肽-1受体激动剂（GLP-1RAs）在肥胖治疗中显示出超越其最初为2型糖尿病管理而开发的显著疗效。本研究通过为期5年的随访，全面探讨了肥胖人群使用GLP-1RAs与癌症发病率之间的关系。 方法：我们利用TriNetX美国协作网络数据库（2013-2023年）开展了一项大规模队列研究，纳入成年肥胖患者。研究采用倾向评分匹配法，通过最近邻法将接受GLP-1RA治疗的患者与对照组按1:1进行配对。主要结局指标为5年随访期间的癌症发病率，并针对不同GLP-1RA药物、患者性别及BMI类别进行了亚组分析。 结果：分析显示，与匹配对照组相比，使用GLP-1RAs与多种癌症类型的风险显著降低相关。在胃肠道癌（HR 0.67，95% CI 0.59–0.75）、皮肤癌（HR 0.62，95% CI 0.55–0.70）、乳腺癌（HR 0.72，95% CI 0.64–0.82）、女性生殖系统癌（HR 0.61，95% CI 0.53–0.71）、前列腺癌（HR 0.68，95% CI 0.58–0.80）以及淋巴/造血系统癌症（HR 0.69，95% CI 0.60–0.80）中均观察到显著风险降低。司美格鲁肽表现出更优的保护作用，尤其在胃肠道癌症中（HR 0.45，95% CI 0.37–0.53）。相反，利拉鲁肽与甲状腺癌（HR 1.70，95% CI 1.03–2.82）和呼吸系统癌症（HR 1.62，95% CI 1.13–2.32）的风险增加相关。 结论：本研究为GLP-1RAs在降低癌症风险方面的潜在作用提供了有力证据，其中司美格鲁肽显示出尤为突出的效果。不同GLP-1RA药物间的效应差异凸显了个体化医疗方法的重要性。这些发现对肥胖管理和癌症预防的临床实践及未来研究具有重要启示。
肿瘤(癌症)患者之家