Flausino Lucas E, Carrasco Alexis Germán Murillo, Furuya Tatiane Katsue, Tuan Wen-Jan, Chammas Roger
Center for Translational Research in Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Comprehensive Center for Precision Oncology, Universidade de São Paulo, São Paulo, Brazil.
BMC Cancer. 2025 Mar 25;25(1):542. doi: 10.1186/s12885-025-13966-8.
The role of sodium-glucose co-transporter 2 inhibitor (SGLT2i) drugs in the management of diabetes and cardiovascular disease is well-established, but emerging evidence suggests potential effects on cancer outcomes, including gastrointestinal (GI) cancers. We conducted an extensive, sex-oriented, real-world data analysis to investigate whether SGLT2i can enhance GI cancer outcomes when used alongside standard therapies such as chemotherapy and radiotherapy.
The study applied a retrospective cohort design with data from the TriNetX research database ( https://trinetx.com ), examining GI cancer patients treated with chemotherapy and/or radiotherapy between 2013 and 2023. The intervention cohort consisted of Gl cancer patients who received SGLT2i, while the control cohort did not. A 5-year follow-up period was used, and baseline characteristics were balanced using a 1:1 propensity score matching technique. Cox proportional-hazards and logistic regression models assessed mortality and morbidity risks between the cohorts.
The study included 6,389 male and 3,457 female patients with GI cancer (ICD-10: C15-C25). The use of SGLT2i was significantly associated with improved survival for both male (HR 0.568; 95% CI 0.534-0.605) and female (HR 0.561; 95% CI 0.513-0.614) patients undergoing chemotherapy and/or radiotherapy. SGLT2i use also correlated significantly with lower hospitalisation rates both in male (OR 0.684; 95% CI 0.637-0.734) and female (OR, 0.590; 95% CI 0.536-0.650) patients. The analysis of GI cancer subtypes also demonstrated similar benefits, without significant adverse effects.
Repurposing SGLT2 inhibitors for cancer treatment could potentially improve outcomes for GI cancer patients without causing significant side effects. Further clinical trials are needed to confirm these findings and establish the optimal condition for its application in GI cancer treatment.
钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）药物在糖尿病和心血管疾病管理中的作用已得到充分确立，但新出现的证据表明其对癌症结局有潜在影响，包括胃肠道（GI）癌症。我们进行了一项广泛的、以性别为导向的真实世界数据分析，以研究SGLT2i与化疗和放疗等标准疗法联合使用时是否能改善胃肠道癌症结局。
该研究采用回顾性队列设计，数据来自TriNetX研究数据库（https://trinetx.com），研究2013年至2023年间接受化疗和/或放疗的胃肠道癌症患者。干预队列由接受SGLT2i的胃肠道癌症患者组成，而对照组未接受。采用5年随访期，并使用1:1倾向评分匹配技术平衡基线特征。Cox比例风险模型和逻辑回归模型评估了队列之间的死亡率和发病率风险。
该研究纳入了6389例男性和3457例女性胃肠道癌症患者（ICD-10：C15-C25）。对于接受化疗和/或放疗的男性（HR 0.568；95%CI 0.534-0.605）和女性（HR 0.561；95%CI 0.513-0.614）患者，使用SGLT2i与生存率提高显著相关。SGLT2i的使用在男性（OR 0.684；95%CI 0.637-0.734）和女性（OR 0.590；95%CI 0.536-0.650）患者中也与较低的住院率显著相关。对胃肠道癌症亚型的分析也显示了类似的益处，且无明显不良反应。
将SGLT2抑制剂重新用于癌症治疗可能会改善胃肠道癌症患者的结局，且不会引起明显副作用。需要进一步的临床试验来证实这些发现，并确定其在胃肠道癌症治疗中的最佳应用条件。
