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

RATIONALE &

OBJECTIVE

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) provide cardiovascular and renal benefits in individuals with or without type 2 diabetes. This systematic review and meta-analysis investigated the risks of acute kidney injury and other adverse events (AEs) associated with SGLT2is across diverse populations.

STUDY

DESIGN

Systematic review and meta-analysis of randomized controlled trials (RCTs).

SETTING & STUDY POPULATIONS: Thirteen RCTs comprising 84,581 participants were included. The studies encompassed diverse populations, varying in diabetes status, presence of chronic kidney disease, and SGLT2i dosages.

SELECTION CRITERIA FOR STUDIES: We included RCTs published through December 31, 2023, that evaluated the safety and efficacy of SGLT2is and reported renal and nonrenal adverse outcomes.

DATA EXTRACTION: Two reviewers independently extracted data and resolved discrepancies by consensus, focusing on renal and nonrenal AEs and subgroup analyses.

ANALYTICAL APPROACH: Random-effects meta-analysis was performed to estimate pooled relative risks or odds ratios with 95% confidence intervals (CIs). Heterogeneity was assessed using the I2 statistic.

RESULTS

SGLT2is were associated with a 20% reduction in the risk of acute kidney injury (relative risk, 0.80; 95% CI, 0.74-0.87), with low between-study heterogeneity, supporting a consistent renoprotective effect. Among patients with chronic kidney disease, the risk of renal composite outcomes was also significantly reduced (odds ratio, 0.70; 95% CI, 0.62-0.79). However, treatment was associated with increased risks of genital infections (P < 0.001), urinary tract infections (P = 0.03), diabetic ketoacidosis (P < 0.001), and hypovolemia (P = 0.008). No significant differences were observed for hypoglycemia (P = 0.08) or lower limb amputation (P = 0.07).

LIMITATIONS: Variability in study design, definitions of AEs, and patient baseline characteristics may influence the findings.

CONCLUSIONS

SGLT2is conferred substantial renoprotective benefits but increases the risk of certain nonrenal AEs. Tailored treatment and close monitoring are crucial to ensure safety and efficacy, especially in high-risk patients.