Sodium-Glucose Cotransporter 2 Inhibitors and Kidney Outcomes across the Spectrum of Kidney Disease: A Systematic Review and Meta-Analysis.

Summary

In a meta-analysis of 10 large RCTs (n=78,184; median follow-up 2.7 years), SGLT2 inhibitors reduced composite kidney outcomes across KDIGO risk categories (HR range ~0.48–0.60) and UACR strata (HR ~0.61–0.80), without heterogeneity between groups. Benefits extended to lower-risk populations, though standardization of composites varied and non-diabetic representation was limited.

Key Findings

• Meta-analysis of 10 RCTs (n=78,184) showed SGLT2 inhibitors reduced composite kidney outcomes across KDIGO low to very high risk groups (HR ~0.48–0.60).
• Benefits were consistent across UACR categories (<30, 30–300, >300 mg/g) with HRs ~0.61–0.80 and no heterogeneity between groups.
• Risk of bias was low; GRADE applied; registration CRD42023492877. Limitations include limited representation of non-diabetic low-risk populations and varying composite definitions.

Clinical Implications

Supports prescribing SGLT2 inhibitors for kidney protection across KDIGO classes and albuminuria levels, with careful consideration of patient profiles and outcome definitions.

Limitations

• Composite kidney outcomes were not standardized across trials.
• Lower representation of non-diabetic low-risk participants limits generalization to that subgroup.

Future Directions

Harmonize outcome definitions and expand trials in non-diabetic, lower-risk cohorts; assess cost-effectiveness and implementation in diverse healthcare systems.