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Combination therapy with mineralocorticoid receptor antagonists and SGLT2 inhibitors versus SGLT2 inhibitor monotherapy in chronic kidney disease: an updated meta-analysis of randomized controlled trials

Muhammad Daniyal S, Ajaz H, Riaz M, Murad Khatoon N, Aftab Z, Tauqir Gondal H, Gul I, Sarwar M et al.

BMC nephrology, 2025

808 participants · 1 citation

Abstract

BACKGROUND: Chronic kidney disease (CKD) affects millions worldwide and poses a major healthcare challenge. While both sodium-glucose co-transporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) or aldosterone synthase inhibitors (ASIs) have shown individual benefits in CKD, data on their combined use remain limited. This study examined the safety and efficacy of combining an SGLT2 inhibitor with an MRA or ASI compared to SGLT2 inhibitor monotherapy. METHODS: A comprehensive search was conducted on PubMed, Cochrane (CENTRAL), ScienceDirect, and Embase for randomized controlled trials (RCTs) comparing combination therapy with an MRA or ASI and an SGLT2 inhibitor with SGLT2 inhibitor monotherapy in patients with CKD. Continuous and dichotomous outcomes were pooled as Mean Difference (MD) or Risk Ratio (RR), respectively, with 95% Confidence Intervals (CIs) using Review Manager (v5.4.1.), and heterogeneity was assessed using the I² statistic. RESULTS: Five RCTs (n = 808 patients) were included. Combination therapy significantly reduced albuminuria (MD: -32.82% [95% CI: -39.16, -26.48] %; p < 0.001), systolic blood pressure (MD: -5.02 mm Hg [95% CI: -6.95, -3.08] mm Hg; p < 0.001), and estimated glomerular filtration rate (MD: -2.59 mL/min/1.73 m2 [95% CI: −3.78, − 1.40] mL/min/1.73 m2; p < 0.001). While the risk of hyperkalemia was higher (RR: 1.91 [95% CI: 1.10,3.33]; p = 0.02) with combination therapy, no significant differences were found in serious…

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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 808 participants or records.

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