Effects of Sodium Glucose Cotransporter 2 Inhibitors by Diabetes Status and Level of Albuminuria: A Meta-Analysis.

Summary

Across 8 RCTs with 58,816 participants, SGLT2 inhibitors reduced kidney disease progression, AKI, any hospitalization, and deaths in both diabetic and non-diabetic CKD, with absolute benefits present across UACR strata and larger for high UACR. Benefits persisted in non–heart failure populations and eGFR <60 mL/min/1.73 m2.

Key Findings

• Reduced kidney disease progression with SGLT2i vs placebo in diabetes (HR 0.65) and without diabetes (HR 0.74).
• Lower rates of AKI (HR ~0.77 with diabetes; 0.72 without), any hospitalization (HR ~0.90), and any death (HR 0.86 with diabetes; trend without).
• Absolute benefits present across UACR strata, with larger absolute kidney benefits at UACR ≥200 mg/g; benefits persisted at eGFR <60 and in non-HF populations.

Clinical Implications

Cardiologists should consider SGLT2 inhibitors for CKD patients regardless of diabetes and UACR to reduce hospitalizations and mortality, coordinating with nephrology, especially in those with higher albuminuria where absolute benefits are larger.

Limitations

• Trial-level (not individual patient) meta-analysis limits subgroup granularity and adjustment.
• Heterogeneity in trial populations and endpoints; mortality reduction less certain in non-diabetic subgroup.

Future Directions

Individual patient data meta-analyses to refine risk-based absolute benefit estimates and pragmatic trials to optimize SGLT2 deployment across CKD phenotypes co-managed by cardiology and nephrology.