Risk of volume reduction associated with sodium-glucose cotransporter-2 inhibitors treatment: a meta-analysis of randomized controlled trials

Abstract

Introduction Sodium-glucose cotransporter-2 (SGLT2) inhibitors is a newly class of drug which improving glycemia by enhancing glycosuria, subsequently reducing blood pressure by osmotic diuresis and natriuresis. There are multiple large-scale randomized control trials demonstrating that SGLT2 inhibitors had salutary effect on cardiovascular-renal outcome, especially on heart failure. Although SGLT2 inhibitors exhibited promising potential value on treatment for type 2 diabetes mellitus (T2DM) with cardiovascular-renal comorbidities, the potential adverse events (AEs) related to osmotic diuresis such as volume reduction should not be neglected. Moreover, older individuals, those with moderate renal impairment, and those receiving antihypertensive therapies are susceptible to adverse events related to volume reduction. Purpose To assess the association between sodium-glucose cotransporter-2 inhibitors and risk of volume reduction in patients with type 2 diabetes mellitus. Methods A systematic literature retrieval was performed in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception up to 10 December 2019, Data for study characteristics and outcomes of interest were extracted from each eligible study. Pooled risk ratios (RRs) with 95% confidence interval (CI) for volume reduction was calculated using random-effects model. Result A total of 51 studies (n=56,866) were included in our meta-analysis, with a result of 1,337 incident volume reduction cases (814 in the SGLT2 inhibitors group, 523 in the control group). The pooled RR was 1.15 (95% CI: 1.03–1.28). It is evident that receiving SGLT2 inhibitors had increased the risk of volume reduction, when stratified by placebo-control or active-control the result was consistent. Conclusion Our meta-analysis has demonstrated that SGLT2 inhibitors increase the risk of volume reduction in patients with T2DM. It is necessary to attention for the risk of volume reduction associated with SGLT2 inhibitors, especially in older individuals, those with moderate renal impairment, and those receiving antihypertensive therapies. SGLT2 inhibitors vs control Funding Acknowledgement Type of funding source: None