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Sodium-Glucose Cotransporter-2 Inhibitors and Acute Kidney Injury Risk: A Systematic Review and Meta-Analysis of

Yu-Cheng Chiang1, Dao-Fu Dai2, Yi-Wen Chiu3

  • 1Department of Medical Education, Cathay General Hospital, Taiwan.

Kidney Medicine
|March 2, 2026
PubMed
Abstract

Insights

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) significantly reduce acute kidney injury risk, offering renoprotective benefits. However, they are linked to increased risks of infections and diabetic ketoacidosis, necessitating careful patient monitoring.

Area of Science:

  • Cardiovascular Medicine
  • Nephrology
  • Pharmacology

Background:

  • Sodium-glucose cotransporter-2 inhibitors (SGLT2is) demonstrate cardiovascular and renal protective effects.
  • Their safety profile, particularly regarding acute kidney injury (AKI) and other adverse events (AEs), requires comprehensive evaluation across diverse patient groups.

Purpose of the Study:

  • To systematically review and meta-analyze randomized controlled trials (RCTs) evaluating the risks of AKI and other AEs associated with SGLT2is.
  • To assess the efficacy and safety of SGLT2is in various populations, including those with and without type 2 diabetes and chronic kidney disease (CKD).

Main Methods:

  • A systematic review and meta-analysis of 13 RCTs involving 84,581 participants, published up to December 31, 2023.
  • Data extraction by two independent reviewers, focusing on renal and nonrenal AEs.
  • Random-effects meta-analysis to calculate pooled relative risks and odds ratios with 95% confidence intervals (CIs).

Main Results:

  • SGLT2is were associated with a 20% reduction in AKI risk (RR, 0.80; 95% CI, 0.74-0.87) with low heterogeneity.
  • In patients with CKD, SGLT2is significantly reduced renal composite outcomes (OR, 0.70; 95% CI, 0.62-0.79).
  • Increased risks were observed for genital infections, urinary tract infections, diabetic ketoacidosis, and hypovolemia, while no significant differences were found for hypoglycemia or lower limb amputation.

Conclusions:

  • SGLT2is provide significant renoprotective benefits, reducing AKI and renal composite outcomes.
  • The benefits must be weighed against increased risks of specific nonrenal AEs, including infections and diabetic ketoacidosis.
  • Tailored treatment strategies and close monitoring are essential for optimizing SGLT2i safety and efficacy, particularly in high-risk individuals.
Keywords:
SGLT2 inhibitorsacute kidney injurychronic kidney diseasekidney failurerenal protection

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