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 I 2 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. Plain-language Summary Doctors are exploring new ways to protect the kidneys, especially in people at risk for acute kidney injury (AKI), a sudden loss of kidney function. Medications called sodium-glucose cotransporter-2 inhibitors (SGLT2is), first used to treat diabetes, have shown promise for kidney and heart protection. We reviewed data from major clinical trials to see if these drugs help lower the risk of AKI. Our findings showed that people who took SGLT2is were less likely to experience AKI, even if they did not have diabetes. However, some users experienced more side effects, like dehydration or infections. These results suggest that SGLT2is may help protect the kidneys when used carefully, particularly in people already at higher risk for kidney problems.