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

Abstract

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].