钠-葡萄糖共转运蛋白 2 抑制剂与癌症：系统评价和荟萃分析。
Sodium-glucose cotransporter 2 inhibitors and cancer: a systematic review and meta-analysis.
机构信息
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.
出版信息
J Endocrinol Invest. 2024 Oct;47(10):2421-2436. doi: 10.1007/s40618-024-02351-0. Epub 2024 Mar 26.
BACKGROUND
The effect of sodium-glucose cotransporter 2 (SGLT2) inhibitors on cancer has yet to be fully elucidated.
OBJECTIVE
This systematic review and meta-analysis investigated the effects of SGLT2 inhibitors on cancer.
METHODS
We searched the PubMed and ClinicalTrials.gov databases up to July 15, 2023, to identify eligible randomized, double-blind, placebo-controlled trials that lasted at least ≥24 weeks. The primary outcome was the overall cancer incidence, and the secondary outcomes were the incidences of various types of cancer. We used the Mantel-Haenszel method, fixed effects model, risk ratio (RR) and 95% confidence interval (CI) to analyze dichotomous variables. Subgroup analysis was performed based on the SGLT2 inhibitor type, baseline conditions, and follow-up duration. All meta-analyses were performed using RevMan5.4.1 and Stata MP 16.0.
RESULTS
A total of 58 publications (59 trials) were included, comprising 113,909 participants with type 2 diabetes mellitus and/or chronic kidney disease and/or high cardiovascular risk and/or heart failure (SGLT2 inhibitor group, 63864; placebo group, 50045). Compared to the placebo SGLT2 inhibitors did not significantly increase the overall incidence of cancer (RR 1.01; 95% CI 0.94-1.08; p = 0.82). However, ertugliflozin did significantly increase the overall incidence of cancer (RR 1.29; 95% CI 1.01-1.64; p = 0.04). SGLT2 inhibitors did not increase the risks of bladder or breast cancer. However, dapagliflozin did significantly reduce the risk of bladder cancer by 47% (RR 0.53; 95% CI 0.35-0.81; p = 0.003). SGLT2 inhibitors had no significant effect on the risks of gastrointestinal, thyroid, skin, respiratory, prostate, uterine/endometrial, hepatic and pancreatic cancers. Dapagliflozin reduced the risk of respiratory cancer by 26% (RR 0.74; 95% CI 0.55-1.00; p = 0.05). SGLT2 inhibitors (particularly mediated by dapagliflozin and ertugliflozin but not statistically significant) were associated with a greater risk of renal cancer than the placebo (RR 1.39; 95% CI 1.04-1.87; p = 0.03).
CONCLUSION
SGLT2 inhibitors did not significantly increase the overall risk of cancer or the risks of bladder and breast cancers. However, the higher risk of renal cancer associated with SGLT2 inhibitors warrants concern.
背景
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂对癌症的影响尚未完全阐明。
目的
本系统评价和荟萃分析旨在研究 SGLT2 抑制剂对癌症的影响。
方法
我们检索了 PubMed 和 ClinicalTrials.gov 数据库，截至 2023 年 7 月 15 日，以确定符合条件的随机、双盲、安慰剂对照试验，这些试验的持续时间至少≥24 周。主要结局是总体癌症发病率，次要结局是各种类型癌症的发病率。我们使用 Mantel-Haenszel 法、固定效应模型、风险比（RR）和 95%置信区间（CI）分析二分类变量。根据 SGLT2 抑制剂类型、基线情况和随访时间进行亚组分析。所有荟萃分析均使用 RevMan5.4.1 和 Stata MP 16.0 进行。
结果
共纳入 58 篇文献（59 项试验），包括 113909 例患有 2 型糖尿病、慢性肾脏病、高心血管风险和心力衰竭的患者（SGLT2 抑制剂组 63864 例，安慰剂组 50045 例）。与安慰剂相比，SGLT2 抑制剂并未显著增加癌症的总体发病率（RR 1.01；95%CI 0.94-1.08；p=0.82）。然而，埃格列净确实显著增加了癌症的总体发病率（RR 1.29；95%CI 1.01-1.64；p=0.04）。SGLT2 抑制剂并未增加膀胱癌或乳腺癌的风险。然而，达格列净显著降低了 47%的膀胱癌风险（RR 0.53；95%CI 0.35-0.81；p=0.003）。SGLT2 抑制剂对胃肠道、甲状腺、皮肤、呼吸道、前列腺、子宫/子宫内膜、肝脏和胰腺癌症的风险没有显著影响。达格列净降低了 26%的呼吸道癌症风险（RR 0.74；95%CI 0.55-1.00；p=0.05）。SGLT2 抑制剂（特别是达格列净和埃格列净介导的，但无统计学意义）与安慰剂相比，与更高的肾癌风险相关（RR 1.39；95%CI 1.04-1.87；p=0.03）。
结论
SGLT2 抑制剂并未显著增加癌症的总体风险或膀胱癌和乳腺癌的风险。然而，SGLT2 抑制剂与更高的肾癌风险相关，值得关注。
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