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Background <p>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.</p> Methods <p>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.</p> Results <p>Five RCTs (<i>n</i> = 808 patients) were included. Combination therapy significantly reduced albuminuria (MD: -32.82% [95% CI: -39.16, -26.48] %; <i>p</i> &lt; 0.001), systolic blood pressure (MD: -5.02&#xa0;mm Hg [95% CI: -6.95, -3.08] mm Hg; <i>p</i> &lt; 0.001), and estimated glomerular filtration rate (MD: -2.59 mL/min/1.73 m<sup>2</sup> [95% CI: −3.78, − 1.40] mL/min/1.73 m<sup>2</sup>; <i>p</i> &lt; 0.001). While the risk of hyperkalemia was higher (RR: 1.91 [95% CI: 1.10,3.33]; <i>p</i> = 0.02) with combination therapy, no significant differences were found in serious adverse events (RR: 0.95 [95% CI: 0.57,1.59]; <i>p</i> = 0.86).</p> Conclusion <p>The combination therapy provides added renal and cardiovascular benefits in CKD without increasing serious adverse effects. These findings support its superior therapeutic potential and highlight the need for large-scale, prospective studies to assess long-term effects on hard renal and cardiovascular outcomes.</p> Prospero registration <p>CRD420251106173.</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月22日

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  • Shaikh Muhammad Daniyal,
  • Hareem Ajaz,
  • Minahil Riaz,
  • Naveen Murad Khatoon,
  • Zunaira Aftab,
  • Habiba Tauqir Gondal,
  • Isbah Gul,
  • Mahwish Sarwar,
  • Fizza Batool,
  • Syeda Laiba Fahim,
  • Amna Noor,
  • Ayan Khalid,
  • Danish Ali Ashraf,
  • Romal Jabarkhil

摘要

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 adverse events (RR: 0.95 [95% CI: 0.57,1.59]; p = 0.86).

Conclusion

The combination therapy provides added renal and cardiovascular benefits in CKD without increasing serious adverse effects. These findings support its superior therapeutic potential and highlight the need for large-scale, prospective studies to assess long-term effects on hard renal and cardiovascular outcomes.

Prospero registration

CRD420251106173.