META-ANALYTIC EVALUATION OF SGLT2 INHIBITORS AND RAAS BLOCKADE IN CHRONIC KIDNEY DISEASE: A SYNERGISTIC STRATEGY FOR RENOPROTECTION

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META-ANALYTIC EVALUATION OF SGLT2 INHIBITORS AND RAAS BLOCKADE IN CHRONIC KIDNEY DISEASE: A SYNERGISTIC STRATEGY FOR RENOPROTECTION

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Co-author 1

Ahmad Naseer Kaihan ahmadnaseerkaihan786@gmail.com Balkh University Faculty of Medicine Internal Medicine Mazar-e-sharif Afghanistan (Islamic Republic of) -

Co-author 2

Sulaiman Kaihan abkaihan1@gmail.com Rahnaward Medical Faculty Internal Medicine Mazar-e-sharif Afghanistan (Islamic Republic of) -

Co-author 3

Hashmat Ullah Faizi Hashmatfaizy3@gmail.com Nangarhar medical faculty Internal Medicine Nangarhar Afghanistan (Islamic Republic of) -

Co-author 4

Ahmad Baseer Kaihan baseer_kaihan2@yahoo.com Balkh University Faculty of Medicine Internal Medicine Mazar-e-Sharif Afghanistan (Islamic Republic of) *

Co-author 5

Amina Kaihan abkaihan2@gmail.com Kabul University of Medical Sciences Stomatology Kabul Afghanistan (Islamic Republic of) -

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Introduction

Sodium-glucose co-transporter 2 (SGLT2) inhibitors and RAAS blockade are now integral to chronic kidney disease (CKD) management. However, the comparative and combined efficacy of these therapies in slowing CKD progression remains incompletely quantified across clinical trials.To evaluate the pooled renal benefits of dapagliflozin, empagliflozin, and RAAS inhibitors individually and in combination, using meta-analytic synthesis of randomized controlled trials (RCTs).

Methods

We conducted a systematic review and meta-analysis of 31 RCTs (2008–2025), involving over 64,000 patients with CKD, with or without diabetes. Studies reporting renal composite outcomes (e.g., sustained eGFR decline, kidney failure, or renal death) were included. Random-effects models generated pooled hazard ratios (HRs) and 95% confidence intervals (CI). Subgroup and sensitivity analyses addressed heterogeneity.

Results

· Dapagliflozin reduced renal risk by 30% (HR: 0.70; 95% CI: 0.62–0.79).

· Empagliflozin showed a 25% risk reduction (HR: 0.75; 95% CI: 0.66–0.85).

· RAAS inhibitors provided a 18% benefit (HR: 0.82; 95% CI: 0.74–0.91).

· Combination therapy (SGLT2i + RAAS blockade) yielded additive protection (HR: 0.68; 95% CI: 0.58–0.79).

The combination consistently outperformed monotherapy across age, eGFR, and proteinuria subgroups, with no excess harm.

Conclusion

Both SGLT2 inhibitors and RAAS blockers independently reduce renal risk in CKD. Their combination confers synergistic benefit, supporting dual therapy as a frontline strategy for slowing CKD progression.

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