Background

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of oral anti-hyperglycemic agents that have been available on the market in Japan since 2014. Although safety information has accumulated alongside the clinical use, the warnings issued by each country based on adverse events associated with the drug are different and examination of the safety of the drug is insufficient.

Objective

This study examined the safety of SGLT2 inhibitors by using a Japanese spontaneous reporting database and focusing on the cautions issued in each country and the disparities within existing research into the occurrence of the adverse events of acute renal failure (ARF), ketoacidosis, and urogenital tract infections (UTIs).

Patients and Methods

We analyzed data recorded on the Japanese Adverse Drug Event Report database (JADER) between April 2014 and February 2019. We calculated the reporting odds ratio (ROR) and 95% confidence interval (CI) with sex and age as adjustment factors.

Results

JADER contained 366,501 cases with the adverse events of interest; 4322 involved SGLT2 inhibitors. The ROR for SGLT2 inhibitors was calculated as 1.0 (95% CI 0.9–1.2) for ARF, 72.2 (95% CI 59.3–87.8) for ketoacidosis, and 14.0 (95% CI 11.0–17.8) for UTIs. Analysis of only subjects receiving treatment for diabetes showed a similar trend.

Conclusion

The results suggested a correlation between SGLT2 inhibitors and the onset of ketoacidosis and UTIs, but not between SGLT2 inhibitors and ARF. Further verification of the safety of SGLT2 inhibitors, through continued risk assessments and large-scale clinical studies, are necessary.

中文翻译：

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SGLT2抑制剂引起的急性肾衰竭，酮症酸中毒和泌尿生殖道感染：使用日本自发报告数据库的信号检测。

背景

钠葡萄糖共转运蛋白2（SGLT2）抑制剂是一类口服抗降血糖药，自2014年以来在日本上市。尽管安全信息已随临床使用而积累，但每个国家/地区都基于不良反应发出警告与药物有关的事件不同，并且对药物安全性的检查不足。

目的

这项研究通过使用日本自发报告数据库并关注每个国家/地区发出的警告以及现有研究中关于急性肾衰竭（ARF），酮酸中毒和泌尿生殖道不良事件发生的差异，研究了SGLT2抑制剂的安全性。感染（UTI）。

患者和方法

我们分析了2014年4月至2019年2月在日本不良药品事件报告数据库（JADER）中记录的数据。我们以性别和年龄为调整因子，计算了报告的优势比（ROR）和95％置信区间（CI）。

结果

JADER收录了366,501例与不良事件有关的病例；4322涉及SGLT2抑制剂。SGLT2抑制剂的ROR计算为ARF为1.0（95％CI 0.9–1.2），酮酸中毒为72.2（95％CI 59.3-87.8），UTIs为14.0（95％CI 11.0-17.8）。仅接受糖尿病治疗的受试者的分析显示出相似的趋势。

结论

结果表明SGLT2抑制剂与酮症酸中毒和UTIs的发作之间存在相关性，但SGLT2抑制剂与ARF之间没有相关性。必须通过持续的风险评估和大规模的临床研究来进一步验证SGLT2抑制剂的安全性。