SGLT2 Inhibitors and Kidney Outcomes by Glomerular Filtration Rate and Albuminuria: A Meta-Analysis

Area of Science:

• Nephrology
• Cardiology
• Endocrinology

Background:

• Sodium-glucose cotransporter 2 (SGLT2) inhibitors are established treatments for chronic kidney disease (CKD) in patients with type 2 diabetes, CKD, or heart failure.
• Uncertainty exists regarding their efficacy in patients with advanced CKD (stage 4) or low levels of albuminuria.

Purpose of the Study:

• To investigate whether baseline estimated glomerular filtration rate (eGFR) or albuminuria levels modify the kidney-protective effects of SGLT2 inhibitors.
• To assess the impact of SGLT2 inhibitors on CKD progression and kidney failure across diverse patient subgroups.

Main Methods:

• A meta-analysis of randomized, double-blind, placebo-controlled trials within the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium (SMART-C).
• Included trials involved at least 500 participants per group, focused on reducing CKD progression, and had a follow-up of at least 6 months.
• Pooled treatment effects using inverse variance-weighted meta-analysis to evaluate CKD progression (kidney failure, ≥50% eGFR reduction, or death from kidney failure), annual eGFR decline, and kidney failure.

Main Results:

• Analysis of 70,361 participants across 10 trials showed SGLT2 inhibitors significantly reduced CKD progression risk (HR, 0.62).
• This benefit was consistent across all baseline eGFR categories (≥60, 45-<60, 30-<45, <30 mL/min/1.73 m2) and albuminuria levels (≤30, >30-300, >300 mg/g).
• SGLT2 inhibitors also slowed the annual eGFR decline and reduced the risk of kidney failure (HR, 0.66) irrespective of baseline kidney function or albuminuria.

Conclusions:

• SGLT2 inhibitors demonstrate robust efficacy in reducing CKD progression and kidney failure.
• These benefits are observed across the entire spectrum of kidney function and albuminuria, including patients with stage 4 CKD or minimal albuminuria.
• Findings support the routine use of SGLT2 inhibitors for improving kidney outcomes in patients with type 2 diabetes, CKD, or heart failure.