Aboukaoud Mohammed, Morhi Yocheved, Osher Ester
Division of Internal Medicine, Rambam Health Care Campus, Haifa, Israel.
Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv, Israel.
Ann Pharmacother. 2025 Oct;59(10):891-903. doi: 10.1177/10600280241312432. Epub 2025 Jan 30.
There is limited knowledge about severe urinary tract infections associated with SGLT2i, despite this being the basis for the Food and Drug Administration (FDA) warning. We aim to provide real-world evidence to clarify this relationship further.
A literature review was performed in PubMed and Embase for cohort studies published up to August 2024 using PICO-consistent terms.
Cohort studies in English involving new users of SGLT2i that compare SGLT2i with glucagon-like receptor agonists (GLP-1RA), DPP4i, and other glucose-lowering medications and report severe urinary tract infection (UTI).
The random-effect model determined the odds ratio (OR) and 95% confidence interval (CI) for severe UTI. Subgroup analysis and meta-regression were used to identify sources of heterogeneity. In 11 cohort studies involving 679 617 individuals with type 2 diabetes mellitus and a median age of 64 (interquartile range [IQR] = 56-72) and 42% (IQR = 39%-51%) females, it was found that the use of SGLT2i was associated with a reduced risk of severe UTI compared with both composite glucose-lowering medications (OR = 0.73, 95% CI = 0.60-0.88) and DPP4i (OR = 0.48, 95% CI = 0.43-0.54). There was no significant difference in the risk compared with GLP-1RA (OR = 0.94, 95% CI = 0.78-1.14).
The lack of increased risk for severe UTI reassures physicians when assessing benefit-risk to continue SGLT2i after a severe UTI. This may enhance patient adherence and improve diabetes management. Furthermore, our findings show no significant risk increase in chronic kidney disease (CKD) patients who would benefit significantly from SGLT2i.
SGLT2i does not appear to pose a greater risk of severe UTI than other oral glucose-lowering medications. This contributes to the existing literature on UTI, accounting for the event's severity. However, more data are needed to assess the potential association between SGLT2i and life-threatening UTI events.
尽管美国食品药品监督管理局（FDA）发出了警告，但关于与钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）相关的严重尿路感染的了解有限。我们旨在提供真实世界证据以进一步阐明这种关系。
在PubMed和Embase中进行文献综述，检索截至2024年8月发表的队列研究，使用与PICO一致的术语。
纳入英文队列研究，涉及SGLT2i新使用者，将SGLT2i与胰高血糖素样肽受体激动剂（GLP-1RA）、二肽基肽酶4抑制剂（DPP4i）及其他降糖药物进行比较，并报告严重尿路感染（UTI）情况。
随机效应模型确定严重UTI的比值比（OR）和95%置信区间（CI）。采用亚组分析和Meta回归识别异质性来源。在11项队列研究中，涉及679617例2型糖尿病患者，中位年龄64岁（四分位间距[IQR]=56 - 72），女性占42%（IQR = 39% - 51%），发现与复合降糖药物相比，使用SGLT2i与严重UTI风险降低相关（OR = 0.73，95% CI = 0.60 - 0.88），与DPP4i相比（OR = 0.48，95% CI = 0.43 - 0.54）。与GLP-1RA相比，风险无显著差异（OR = 0.94，95% CI = 0.78 - 1.14）。
严重UTI风险未增加，这让医生在评估严重UTI后继续使用SGLT2i的获益风险时感到安心。这可能会提高患者依从性并改善糖尿病管理。此外，我们的研究结果表明，从SGLT2i中显著获益的慢性肾脏病（CKD）患者的风险没有显著增加。
SGLT2i似乎不会比其他口服降糖药物带来更高的严重UTI风险。这为关于UTI的现有文献做出了贡献，考虑到了该事件的严重性。然而，需要更多数据来评估SGLT2i与危及生命的UTI事件之间的潜在关联。
