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Meta-Analysis
. 2023 Mar;60(3):325-335.
doi: 10.1007/s00592-022-01989-7. Epub 2022 Nov 1.

Effects of sodium-glucose co-transporter-2 inhibitors on kidney, cardiovascular, and safety outcomes in patients with advanced chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials

Haiyan Cao #  1 , Xiaosheng Rao #  2 , Junya Jia  1 , Tiekun Yan  1 , Dong Li  3
Affiliations
Meta-Analysis

Effects of sodium-glucose co-transporter-2 inhibitors on kidney, cardiovascular, and safety outcomes in patients with advanced chronic kidney disease: a systematic review and meta-analysis of randomized controlled trials

Haiyan Cao et al. Acta Diabetol. 2023 Mar.

Abstract

Aims: The overall effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors in patients with advanced chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR), 15-30 ml/min per 1.73 m2) remain unclear, and we thus conducted a systematic review and meta-analysis to evaluate the effects of SGLT2 inhibitors on kidney, cardiovascular (CV), and safety outcomes in patients with advanced CKD.

Methods: The Medline, Embase, and Cochrane Library databases were systematically searched for randomized controlled trials (RCTs) published up to March 3, 2022, and reporting effects of SGLT2 inhibitors on kidney, CV, or safety outcomes in patients with advanced CKD.

Results: From 2675 records, six RCTs with 2167 participants were included in the quantitative analyses. In patients with advanced CKD, SGLT2 inhibitors reduced the risk of the primary kidney outcome (a composite of worsening kidney function, end-stage kidney disease (ESKD), or kidney death) by 23% (RR 0.77, 95% CI 0.61-0.98, p = 0.04, I2 = 0 for the heterogeneity) and slowed the annual decline in eGFR slope, with the difference between SGLT2 inhibitor group and placebo group being 1.24 mL/min/1.73m2 per year (95% CI 0.06-2.42, p = 0.04). SGLT2 inhibitors were also associated with a decreased risk of primary CV outcome (a composite of CV death or hospitalization for heart failure) (HR 0.71, 95% CI 0.53-0.96, p = 0.03, I2 = 0 for the heterogeneity) and with similar risks of adverse events (such as acute kidney injury, fracture, amputation, and urinary tract infection).

Conclusions: Among patients with advanced CKD, SGLT2 inhibitors reduced the risks of primary kidney and CV outcomes and attenuated the progressive decrease in eGFR compared with placebo, with no evidence of additional safety concerns. These observed benefits may support continuing the use of SGLT2 inhibitors in patients with advanced CKD before initiating maintenance dialysis or kidney transplantation. Future large-scale RCTs are needed to confirm the robustness of these results.

Keywords: Cardiovascular; Chronic kidney disease; Kidney; Meta-analysis; SGLT2 inhibitors; Systematic review.

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