Xu Bo, Liu Yilin, He Zunbo, Zhou Jiecan
The First Affiliated Hospital, Hunan Provincial Clinical Medical Research Center for Drug Evaluation of Major Chronic Diseases, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
The First Affiliated Hospital, Hengyang Clinical Pharmacology Research Center, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
J Endocrinol Invest. 2025 Sep 18. doi: 10.1007/s40618-025-02705-2.
Effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors on genital cancer risk remains unclear.
The objective of this study was to investigate the impact of SGLT2 inhibitors/SGLT2 inhibition on genital cancer risk.
We systematically searched PubMed, Web of Science, EU Clinical Trials Register, and ClinicalTrials.gov for large randomized controlled trials up to June 4, 2025. The Mantel-Haenszel method was applied, with risk ratios (RRs) and 95% confidence intervals (CIs) used for dichotomous outcomes. In the Mendelian randomization study, genetic variants in SLC5A2 served as instrumental variables to investigate the causal relationship between SGLT2 inhibition and genital cancers.
A total of 15 studies (16 trials) involving 101,430 patients were included. SGLT2 inhibitors did not significantly reduce genital cancer risk compared to placebo (RR 1.10; 95% CI 0.93-1.31; P = 0.28; moderate certainty of evidence), with consistent findings across subgroup analyses. No significant effects of SGLT2 inhibitors were observed for cervical, endometrial, ovarian, prostate, uterine, penile, or vulvar cancers. Dapagliflozin potentially increased the risk of male genital cancers (RR 1.31; 95% CI 0.99-1.74; P = 0.06). SGLT2 inhibition significantly reduced testicular [odds ratio (OR) 0.012; 95% CI 0.001-0.220; P = 0.003] and cervical (OR 0.013; 95% CI 0.001-0.122; P = 1.615 × 10 - 4) cancer risks. Pooled results from both discovery and replication cohorts demonstrated that SGLT2 inhibition reduced cervical cancer risk (OR 0.016; 95% CI 0.002-0.116; P < 0.0001).
SGLT2 inhibitors exhibited a neutral overall risk profile for genital cancers, while genetic evidence demonstrated beneficial effects specifically for cervical cancer.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂对生殖系统癌症风险的影响尚不清楚。
本研究旨在调查SGLT2抑制剂/SGLT2抑制对生殖系统癌症风险的影响。
我们系统检索了截至2025年6月4日的PubMed、科学网、欧盟临床试验注册库和ClinicalTrials.gov，以查找大型随机对照试验。采用Mantel-Haenszel方法，二分类结局使用风险比（RR）和95%置信区间（CI）。在孟德尔随机化研究中，溶质载体家族5成员2（SLC5A2）中的基因变异作为工具变量，以研究SGLT2抑制与生殖系统癌症之间的因果关系。
共纳入15项研究（16项试验），涉及101430例患者。与安慰剂相比，SGLT2抑制剂未显著降低生殖系统癌症风险（RR 1.10；95%CI 0.93-1.31；P = 0.28；证据确定性中等），亚组分析结果一致。未观察到SGLT2抑制剂对宫颈癌、子宫内膜癌、卵巢癌、前列腺癌、子宫癌、阴茎癌或外阴癌有显著影响。达格列净可能增加男性生殖系统癌症风险（RR 1.31；95%CI 0.99-1.74；P = 0.06）。SGLT2抑制显著降低睾丸癌[比值比（OR）0.012；95%CI 0.001-0.220；P = 0.003]和宫颈癌（OR 0.013；95%CI 0.001-0.122；P = 1.615×10 - 4）风险。发现队列和重复队列的汇总结果表明，SGLT2抑制降低了宫颈癌风险（OR 0.016；95%CI 0.002-0.116；P < 0.0001）。
SGLT2抑制剂对生殖系统癌症总体风险呈中性，而基因证据表明其对宫颈癌有显著益处。
