Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Kidney Outcomes across Baseline Cardiovascular-Kidney-Metabolic Conditions

Key Points Sodium-glucose cotransporter-2 (SGLT2) inhibitors slowed the rate of eGFR slope decline in patients with heart failure, CKD, and type 2 diabetes mellitus and in all combinations of multimorbid conditions among these diseases. SGLT2 inhibitors decreased kidney composite outcomes among all disease states and different combinations of multimorbidity, except in patients with heart failure with preserved ejection fraction and heart failure without type 2 diabetes mellitus. SGLT2 inhibitors were found to decrease the risk of kidney failure in patients with type 2 diabetes mellitus and also in those with CKD. Background The effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on kidney outcomes in patients with varying combinations of heart failure, CKD, and type 2 diabetes mellitus have not been quantified. Methods PubMed and Scopus were queried up to December 2023 for primary and secondary analyses of placebo-controlled trials of SGLT2is in patients with heart failure, CKD, or type 2 diabetes mellitus. Outcomes of interest were composite kidney end point (combination of eGFR <15 ml/min per 1.73 m 2 , sustained doubling of serum creatinine, varying percent change in eGFR, and need for KRT), rate of eGFR slope decline, and albuminuria progression. Hazard ratios (HRs) and mean differences with their 95% confidence intervals (CIs) were extracted onto an Excel sheet, and the results were then pooled using a random-effect model through Review Manager (version 5.3, Cochrane Collaboration). Results Eleven trials ( n =80,928 patients) were included. Compared with the placebo, SGLT2is reduced the risk of the composite kidney end point by 41% (HR, 0.59; 95% CI, 0.42 to 0.83) in heart failure with reduced ejection fraction, 36% (HR, 0.64; 95% CI, 0.55 to 0.73) in CKD, and 38% (HR, 0.62; 95% CI, 0.56 to 0.69) in type 2 diabetes mellitus. A similar pattern of benefit was observed in combinations of these comorbidities and in patients without baseline heart failure, CKD, or type 2 diabetes mellitus. SGLT2is slowed the rate of eGFR slope decline and reduced the risk of sustained doubling of serum creatinine by 36% (HR, 0.64; 95% CI, 0.56 to 0.72) in the overall population, and a consistent effect on kidney outcomes was observed in most subpopulations with available data. Conclusions SGLT2i improved kidney outcomes in cohorts with heart failure, CKD, and type 2 diabetes mellitus, and these effects were consistent across patients with different combinations of these comorbidities.