The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on renal outcomes in patients with different combinations of chronic kidney disease, heart failure, and type 2 diabetes have not been quantified. To address this gap, Tariq Jamal Siddiqi, MD, and colleagues queried the PubMed and Scopus databases through December 2023 for primary and secondary analyses of placebo-controlled trials of SGLT2i in such patients.
The study outcomes were a composite kidney endpoint (combination of eGFR <15 mL/min/1.73 m2, continuous doubling of serum creatinine, variable percentage change in eGFR, and need for kidney replacement therapy), rate of eGFR slope decline, and albuminuria progression. Hazard ratios and mean differences with 95% confidence intervals were extracted, and the results were pooled using a random-effect model through Review Manager.
Analysis of 11 trials and 80,928 patients found that SGLT2i reduced the risk of the composite kidney endpoint by 41% (HR, 0.59; 95% CI, 0.42-0.83) in heart failure with reduced ejection fraction, 36% (HR, 0.64; 95% CI, 0.55-0.73) in CKD, and 38% (HR, 0.62; 95% CI, 0.56-0.69) in type 2 diabetes compared to the placebo. SGLT2i was similarly beneficial in combinations of the three comorbidities and in patients without heart failure, CKD, or type 2 diabetes at baseline.
SGLT2i also reduced the risk of sustained doubling of serum creatinine by 36% (HR, 0.64; 95% CI, 0.56-0.72) and slowed the rate of eGFR slope decline in the overall population. A consistent positive effect on renal outcomes was observed in most subpopulations with available data.
In conclusion, SGLT2i improved renal outcomes in patients with heart failure, CKD, and type 2 diabetes. The benefits were consistent among patients with different combinations of these comorbidities.
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