Sodium-glucose cotransporter 2 inhibitor increases risk of urinary tract infection: Evidence from mendelian randomization and meta-analysis.

IF 3.1 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Jie Ren, Sining Yang, Yifei Wang, Rui Chen, Xing Zhang, Yang Feng, Fengping Zhang, Yifan Jia, Jingyao Zhang, Chang Liu
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Abstract

Aims: Sodium-glucose cotransporter 2 inhibitor (SGLT2i) is a new hypoglycaemic drug with good effect. However, whether increased urine sugar also increases the risk of urinary tract infection (UTI) is still controversial.

Methods: Mendelian randomization (MR) was used to explore the causal relationships between SGLT2i and UTI. To ensure the robustness of results of MR, we used 3 genome-wide association study (GWAS) datasets of UTI, which equates to 3 randomized controlled trials. Inverse variance weighted (IVW) was the most important method of MR. Sensitivity analysis was used to assess the robustness of MR. We also integrated the results of IVW by meta-analysis to further increase the confidence.

Results: According to IVW, SGLT2i increased the risk of UTI in some results: UTI (odds ratio [OR]: 1.015, 95% confidence interval [CI]: 1.008-1.023, P = 7.121E-05); UTI (OR: 1.008, 95%CI: 1.000-1.016, P = .037); However, other result showed SGLT2i did not increase the risk of UTI: UTI (OR: 1.008, 95%CI: 0.996-1.020, P = .190). To further increase the robustness of the results, we integrated the IVW results through meta-analysis. The results of meta-analysis showed SGLT2i increased the risk of UTI (OR: 1.011, 95%CI: 1.006-1.016, P < .001).

Conclusion: SGLT2i increases the risk of UTI. However, SGLT2i should not be abandoned because of the risk of UTI. The use of SGLT2i should be considered with caution only when the diabetes patient requires a high-dose use and has a history of complicated UTI. More clinical and experimental studies are needed to explore the broad effects and mechanisms of SGLT2i.

钠-葡萄糖共转运蛋白2抑制剂增加尿路感染的风险:来自孟德尔随机化和荟萃分析的证据
目的:钠-葡萄糖共转运蛋白2抑制剂(Sodium-glucose cotransporter 2 inhibitor, SGLT2i)是一种效果良好的新型降糖药物。然而,尿糖升高是否也会增加尿路感染(UTI)的风险仍有争议。方法:采用孟德尔随机化(Mendelian randomization, MR)方法探讨SGLT2i与UTI之间的因果关系。为了确保MR结果的稳健性,我们使用了3个UTI全基因组关联研究(GWAS)数据集,相当于3个随机对照试验。反方差加权(Inverse variance weighted, IVW)是mr最重要的方法,我们采用敏感性分析来评估mr的稳健性,并通过meta分析对IVW结果进行整合,以进一步提高可信度。结果:根据IVW, SGLT2i增加了UTI的风险:UTI(优势比[OR]: 1.015, 95%可信区间[CI]: 1.008-1.023, P = 7.121E-05);Uti (or: 1.008, 95%ci: 1.000-1.016, p = 0.037);然而,其他结果显示SGLT2i并未增加UTI的风险:UTI (OR: 1.008, 95%CI: 0.996-1.020, P = 0.190)。为了进一步提高结果的稳健性,我们通过meta分析整合了IVW结果。meta分析结果显示SGLT2i增加UTI风险(OR: 1.011, 95%CI: 1.006-1.016, P)结论:SGLT2i增加UTI风险。然而,SGLT2i不应该因为尿路感染的风险而被放弃。只有当糖尿病患者需要大剂量使用并有复杂尿路感染史时,才应谨慎考虑SGLT2i的使用。需要更多的临床和实验研究来探索SGLT2i的广泛作用和机制。
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来源期刊
CiteScore
6.30
自引率
8.80%
发文量
419
审稿时长
1 months
期刊介绍: Published on behalf of the British Pharmacological Society, the British Journal of Clinical Pharmacology features papers and reports on all aspects of drug action in humans: review articles, mini review articles, original papers, commentaries, editorials and letters. The Journal enjoys a wide readership, bridging the gap between the medical profession, clinical research and the pharmaceutical industry. It also publishes research on new methods, new drugs and new approaches to treatment. The Journal is recognised as one of the leading publications in its field. It is online only, publishes open access research through its OnlineOpen programme and is published monthly.
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