Zheng Zhigui, He Dongyuan, Chen Jianguo, Xie Xiaohui, Lu Yunan, Wu Binbin, Jiang Xinxin
Department of Nephropathy, Zhejiang Hospital, Hangzhou, People's Republic of China.
Clin Drug Investig. 2023 Apr;43(4):209-225. doi: 10.1007/s40261-023-01256-9. Epub 2023 Apr 3.
To investigate whether dapagliflozin (as a selective inhibitor of sodium-glucose cotransporter 2), increases the risk of urinary tract infection (UTI) in the treatment of type 2 diabetes mellitus (T2DM) remains an ongoing issue. We performed a systematic review and meta-analysis of randomized clinical trials (RCTs) to estimate the short-term and long-term risks of UTI in patients with T2DM who received dapagliflozin at different doses.
The PubMed, EMBASE, and the Cochrane Library and ClinicalTrials.gov website were searched up to December 31, 2022. Only RCTs involving adult T2DM patients with a trial duration of at least 12 weeks were included. The data were summarized using random- or fixed-effects models based on overall heterogeneity. A subgroup analysis was also performed. The review protocol was previously registered in the PROSPERO database (CRD42022299899).
In total, 42 RCTs involving 35,938 patients were assessed for eligibility. The results showed that dapagliflozin imposed a higher risk of UTI compared to placebo and other active treatments, with a heterogeneity of 11% (odds ratio [OR] 1.17, 95% CI 1.04-1.31, p = 0.006). In the subgroup analysis, dapagliflozin 10 mg/day with a treatment period of > 24 weeks was associated with a significantly higher UTI risk than placebo or other active treatments (OR 1.27, 95% CI 1.13-1.43, p < 0.0001). The ORs for dapagliflozin as monotherapy and combination therapy in the control group were 1.05 (95% CI 0.88-1.25, p = 0.571) and 1.27 (95% CI 1.09-1.48, p = 0.008), respectively.
High-dose, long-term treatment, and add-on therapy of dapagliflozin call for careful consideration of the risk of UTI in T2DM patients.
探讨达格列净（作为钠-葡萄糖协同转运蛋白2的选择性抑制剂）在治疗2型糖尿病（T2DM）时是否会增加尿路感染（UTI）的风险仍是一个未决问题。我们对随机临床试验（RCT）进行了系统评价和荟萃分析，以评估接受不同剂量达格列净治疗的T2DM患者发生UTI的短期和长期风险。
检索截至2022年12月31日的PubMed、EMBASE、Cochrane图书馆和ClinicalTrials.gov网站。仅纳入涉及成年T2DM患者且试验持续时间至少为12周的RCT。根据总体异质性，使用随机或固定效应模型汇总数据。还进行了亚组分析。该综述方案先前已在PROSPERO数据库（CRD42022299899）中注册。
总共评估了42项涉及35938例患者的RCT的入选资格。结果显示，与安慰剂和其他活性治疗相比，达格列净导致UTI的风险更高，异质性为11%（比值比[OR]1.17，95%置信区间1.04-1.31，p=0.006）。在亚组分析中，治疗期>24周的每日10mg达格列净与UTI风险显著高于安慰剂或其他活性治疗相关（OR 1.27，95%置信区间1.13-1.43，p<0.0001）。达格列净在对照组中作为单药治疗和联合治疗的OR分别为1.05（95%置信区间0.88-1.25，p=0.571）和1.27（95%置信区间1.09-1.48，p=0.008）。
达格列净的高剂量、长期治疗和联合治疗需要仔细考虑T2DM患者发生UTI的风险。
