Table_2_Risk of hypovolemia associated with sodium–glucose cotransporter-2 inhibitors treatment: A meta-analysis of randomized controlled trials.DOCX

Aim of the reviewTo assess the risk of hypovolemia for sodium–glucose cotransporter-2 (SGLT2) inhibitors treatment.
MethodA systematic literature retrieval was performed in PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and Scopus from inception up to 4 October 2022, Data for study characteristics and outcomes of interest were extracted from each eligible study. Risk ratios (RRs) with a 95% confidence interval (CI) for hypovolemia were calculated using a random-effect model.
ResultsA total of 57 studies (n = 68,622) were included in our meta-analysis, with a result of 1,972 hypovolemia incidents (1,142 in the SGLT2 inhibitors group and 830 in the control group). The pooled RR was 1.12 (95% CI: 1.02–1.22). It is evident that receiving SGLT2 inhibitors increased the risk of hypovolemia. When stratified by category of SGLT2 inhibitors the result was consistent; when the subgroup was analyzed by age, the pooled RR was 1.07 (95% CI: 0.94–1.23) in patients aged ≥65 years and 1.14 (95% CI: 1.02–1.28) in those aged <65 years. When comparing the baseline estimated glomerular filtration rate (eGFR) of less than or equal to 60 mL/min/1.73 m2 with a baseline eGFR greater than 60 mL/min/1.73 m2, the pooled RR was 1.21, (95% CI: 1.00–1.46) and 1.08, (95%CI: 0.98–1.20), respectively.
ConclusionOur meta-analysis has demonstrated that SGLT2 inhibitors increased the risk of hypovolemia in patients with Type 2 Diabetes Mellitus (T2DM). It is necessary to pay attention to the risk of hypovolemia associated with SGLT2 inhibitors, especially in older individuals and those with moderate renal impairment.
Systematic review registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42020156254].

本系统评价的研究目的为评估钠-葡萄糖协同转运蛋白2（sodium–glucose cotransporter-2, SGLT2）抑制剂治疗相关的低血容量风险。
研究方法：本研究于PubMed、Embase、Cochrane对照试验中心注册库（Cochrane Central Register of Controlled Trials, CENTRAL）、Web of Science及Scopus数据库开展系统性文献检索，检索时限为各数据库建库至2022年10月4日。从每一项符合纳入标准的研究中提取研究特征及关注结局数据，采用随机效应模型计算低血容量的风险比（risk ratio, RR）与95%置信区间（confidence interval, CI）。
研究结果：本荟萃分析共纳入57项研究，涉及68622例受试者，其中1972例发生低血容量事件（SGLT2抑制剂组1142例，对照组830例）。合并后风险比为1.12（95%CI：1.02~1.22），提示使用SGLT2抑制剂可升高低血容量发生风险。按SGLT2抑制剂类别进行亚组分析，结果保持一致；按年龄分层的亚组分析显示，≥65岁患者的合并RR为1.07（95%CI：0.94~1.23），<65岁患者为1.14（95%CI：1.02~1.28）。按基线估算肾小球滤过率（estimated glomerular filtration rate, eGFR）分层：基线eGFR≤60 mL/min/1.73 m²亚组的合并RR为1.21（95%CI：1.00~1.46），基线eGFR>60 mL/min/1.73 m²亚组为1.08（95%CI：0.98~1.20）。
研究结论：本荟萃分析证实，SGLT2抑制剂可升高2型糖尿病（Type 2 Diabetes Mellitus, T2DM）患者的低血容量发生风险。临床需警惕SGLT2抑制剂相关的低血容量风险，尤其针对老年患者及中度肾功能损害人群。
系统评价注册信息：[https://www.crd.york.ac.uk/prospero/]，注册号[CRD42020156254]。