Ting Liu1, Rui Li2, Xiaoxia Wang2, Xingxing Gao2, Xiaodong Zhang3. 1. Department of Nephrology, The First Hospital of Shanxi Medical University, Taiyuan, China. 2. Shanxi Medical University, Taiyuan, China. 3. Department of Nephrology, The First Hospital of Shanxi Medical University, Taiyuan, China. Electronic address: zxdspl@163.com.
Abstract
BACKGROUND AND OBJECTIVE: Efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in combination with renin-angiotensin-system (RAS) blockers for CKD remains controversial. We conducted this meta-analysis to explore the effect of SGLT2 inhibitors combining with RAS blockers on cardiovascular outcomes in chronic kidney disease (CKD) patients. METHODS: We searched Embase, PubMed, Web of Science, and Cochrane Library databases with the following keywords. "Renal Insufficiency, Chronic" or "Diabetic Nephropathies" and "Sodium-glucose cotransporter 2 inhibitors". We included randomized controlled trials (RCTs) based on angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy. The outcome events included cardiac and renal outcomes and other adverse events. This study is registered with PROSPERO: CRD42020218337. RESULTS: Ten RCTs including 16,983 CKD patients met the inclusion criteria. Compared with placebo plus RAS blockers, SGLT2 inhibitors plus RAS blockers significantly reduced cardiovascular mortality and heart failure-related hospitalization rates (RR=0.78, 95% CI: 0.66-0.91, p=0.002; RR=0.7, 95% CI: 0.61-0.8, p=0.000). We also performed trials sequential analysis (TSA) and the results indicated that our results are reliable. Additionally, it significantly reduced the 24-h urinary albumin excretion rate (24hUAE) and the creatinine elevation rate (WMD=-0.19, 95% CI: -0.24 to -0.14; RR=0.61, 95% CI: 0.51-0.74, p=0.000), delayed progression to end-stage renal disease (ESRD) (RR=0.69, 95% CI: 0.59-0.81, p=0.000). Further, it had no significant effect on the incidence of renal-related adverse events or renal-related mortality. Although it decreased the estimated glomerular filtration rate (eGFR) (WMD=-5.4, 95% CI: -7.24 to -3.57), this effect was reversible. CONCLUSIONS: These data provide a well-document testimonial of the benefits of the combined use of SGLT2 inhibitors and RAS blockers for cardiovascular and renal outcomes in CKD patients.
BACKGROUND AND OBJECTIVE: Efficacy of sodium-glucose cotransporter 2 (SGLT2) inhibitors in combination with renin-angiotensin-system (RAS) blockers for CKD remains controversial. We conducted this meta-analysis to explore the effect of SGLT2 inhibitors combining with RAS blockers on cardiovascular outcomes in chronic kidney disease (CKD) patients. METHODS: We searched Embase, PubMed, Web of Science, and Cochrane Library databases with the following keywords. "Renal Insufficiency, Chronic" or "Diabetic Nephropathies" and "Sodium-glucose cotransporter 2 inhibitors". We included randomized controlled trials (RCTs) based on angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy. The outcome events included cardiac and renal outcomes and other adverse events. This study is registered with PROSPERO: CRD42020218337. RESULTS: Ten RCTs including 16,983 CKD patients met the inclusion criteria. Compared with placebo plus RAS blockers, SGLT2 inhibitors plus RAS blockers significantly reduced cardiovascular mortality and heart failure-related hospitalization rates (RR=0.78, 95% CI: 0.66-0.91, p=0.002; RR=0.7, 95% CI: 0.61-0.8, p=0.000). We also performed trials sequential analysis (TSA) and the results indicated that our results are reliable. Additionally, it significantly reduced the 24-h urinary albumin excretion rate (24hUAE) and the creatinine elevation rate (WMD=-0.19, 95% CI: -0.24 to -0.14; RR=0.61, 95% CI: 0.51-0.74, p=0.000), delayed progression to end-stage renal disease (ESRD) (RR=0.69, 95% CI: 0.59-0.81, p=0.000). Further, it had no significant effect on the incidence of renal-related adverse events or renal-related mortality. Although it decreased the estimated glomerular filtration rate (eGFR) (WMD=-5.4, 95% CI: -7.24 to -3.57), this effect was reversible. CONCLUSIONS: These data provide a well-document testimonial of the benefits of the combined use of SGLT2 inhibitors and RAS blockers for cardiovascular and renal outcomes in CKD patients.