Table 3.
Summary of the main renal outcomes of the SGLT2 inhibitors trials.
| Trial name/drug | Study population | Primary endpoint | Renal outcomes | Effect size (SGLT2i vs. placebo) | Renal benefits vs. placebo | Ref. |
|---|---|---|---|---|---|---|
| the EMPA-REG OUTCOME/empagliflozin | 7,020 T2DM, established cardiovascular disease, with eGFR >30 ml/min/1.73 m² | progression to macroalbuminuria D-Scr, initiation of KRT, or death from renal disease, and incident albuminuria | Doubling of Scr with eGFR ≤45 ml/min/1.73 m2, initiation of KRT, or renal death | HR 0.54 (95%CI 0.40–0.75) | Superior | (159) |
| Incident or worsening nephropathy | HR 0.61(95%CI 0.53–0.70) | |||||
| the CANVAS Program/Canagliflozin | 10,142 T2DM, high cardiovascular risk, with eGFR >30 (ml/min/1.73 m²) | a composite of death from cardiovascular causes, non-fatal myocardial infarction, or nonfatal stroke | At least 40% reduction in eGFR, need for KRT, or renal death | HR 0.60 (95%CI 0.47–0.77) | Superior | (160) |
| Progression of albuminuria | HR 0.73 (95% CI, 0.67–0.79 | |||||
| the CANVAS-R Program/Canagliflozin | 10,142 T2DM | a composite of sustained and adjudicated D-Scr, ESKD, or renal death | D-Scr, ESKD, or renal death | HR 0.53 (95% CI 0·33–0·84) | Superior | (161) |
| 40% reduction in eGFR, ESKD, or death from renal causes | HR 0.60 (95% CI 0·47–0·77) | |||||
| the CREDENCE Trial/Canagliflozin | 4,401 T2DM and albuminuric CKD | D-Scr, ESKD, or renal/CV death | D-Scr, ESKD, or renal/CV death | HR 0.70 (95% CI, 0.59–0.82) | Superior | (162) |
| D-Scr, ESKD, or renal death | HR 0.66 (95% CI, 0.53–0.81) | |||||
| the DECLARE-TIMI 58/Dapagliflozin | 17,160 T2DM | MACE and a composite of cardiovascular death or hospitalization for heart failure | At least 40% reduction in eGFR to less than 60 ml/min per 1.73 m2, ESKD, or renal/CV death | HR 0.76 (95% CI 0.67–0.87) | Superior | (163) |
| At least 40% reduction in eGFR to less than 60 ml/min per 1.73 m2, ESKD, or renal death | HR 0.53 (95% CI 0.43–0.66) | |||||
| DAPD-CKD | 4304 CKD, with eGFR25-75(ml/min/1.73 m²), uACR 200 to 5,000 mg/g | a composite of a sustained decline in the estimated GFR of at least 50%, ESKD, or renal/CV death | Primary outcome | HR 0.61 (95% CI 0.51–0.72) | Superior | (164) |
| Renal-specific composite outcome (D-SCr, ESKD, or renal death) |
HR 0.56 (95% CI, 0.45–0.68) | |||||
| Empire HF Renal trial/Empagliflozin | 391 heart failure patients, LVEF <=40%, with eGFR >30(ml/min/1.73 m²) | the between-group difference in the changes in estimated extracellular volume, estimated plasma volume, and measured GFR from baseline to 12 weeks. | Primary outcomes | reductions in estimated extracellular volume (adjusted mean difference −0.12 L, 95% CI −0.18 to −0.05; p = 0.00056), estimated plasma volume (−7.3%, −10.3 to −4.3; p < 0·0001), and measured GFR (−7.5 ml/min, −11.2 to −3.8; p = 0.00010) | Superior in Fluid volume changes | (165) |
| VERTIS CV trial/ertugliflozin | 8,246 patients with type 2 diabetes and established atherosclerotic cardiovascular disease | a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke (i.e., a major adverse cardiovascular event). | renal-specific composite outcome (D-SCr, ESKD, or renal death) | HR 0.81 (95.8% CI, 0.63 to 1.04) | No significant benefit | (166) |
D-Scr, doubling of the serum creatinine level; KRT, kidney replacement therapy; ESKD, end-stage of kidney disease; LVEF, left ventricular ejection fraction; MACEs, major adverse cardiovascular events defined as cardiovascular death, myocardial infarction, or ischemic stroke; uACR, urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams); HR, hazard ratio.