Safeguarding the Kidneys: SGLT2 Inhibitors Reduce Risk of Acute Kidney Injury—A Systematic Review and Meta-Analysis

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Safeguarding the Kidneys: SGLT2 Inhibitors Reduce Risk of Acute Kidney Injury—A Systematic Review and Meta-Analysis

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Co-author 1

You-Hsien Lin hugoyl@gap.kmu.edu.tw Kaohsiung Medical University Hospital Nephrology Kaohsiung Taiwan *

Co-author 2

Kai-Ting Chang heildberg1008@gmail.com Kaohsiung Medical University Gangshan Hospital Pediatrics Kaohsiung Taiwan -

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Introduction

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) have become a cornerstone in the management of cardiorenal disease, demonstrating efficacy in slowing chronic kidney disease (CKD) progression in patients with or without type 2 diabetes. Despite their well-established benefits, concerns persist regarding their safety, particularly the potential risk of acute kidney injury (AKI) and other non-renal adverse events (AEs). This meta-analysis aimed to evaluate the effects of SGLT2is on the incidence of AKI and a broad range of AEs across diverse clinical populations.

Methods

A systematic review and meta-analysis of 14 randomized controlled trials (RCTs), including 91,601 participants with varying diabetes status, CKD stage, and SGLT2i dosage, was conducted. Studies were selected based on predefined inclusion criteria evaluating renal and non-renal safety outcomes. Two independent reviewers performed data extraction and resolved discrepancies by consensus. A random-effects model was used to calculate pooled relative risks (RRs) or odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic.

Results

SGLT2is significantly reduced the risk of AKI by 21% (RR = 0.79, 95% CI: 0.73–0.86, I² = low), suggesting consistent renoprotective effects. Additional renal outcomes showed benefits for acute renal failure (OR = 0.79), CKD progression (OR = 0.70), and kidney disease progression (OR = 0.67). However, SGLT2is were associated with increased risks of genital infections (p < 0.0001), urinary tract infections (p = 0.03), diabetic ketoacidosis (p < 0.0001), and hypovolemia (p = 0.008). No significant differences were observed for hypoglycemia (p = 0.08) or lower limb amputation (p = 0.07).

Conclusion

SGLT2is demonstrate a robust protective effect against AKI and other renal events across diverse populations. However, the increased risk of select non-renal AEs highlights the need for individualized treatment strategies and close clinical monitoring, particularly in high-risk populations.

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