Selected clinical trials of SGLT2i and SGLT1/2i, empagliflozin, canagliflozin, dapagliflozin, ertugliflozin, and sotagliflozin
| SGLT2i or SGLT1/2i | Trial | Intervention | N | Mean baseline eGFR (mL/min/1.73 m2) | Median follow-up (years) | Primary composite outcome (HR (95% CI)) | Kidney outcome (HR (95% CI)) |
| Empagliflozin | EMPA-REG OUTCOME | Empagliflozin 10 mg once per day, empagliflozin 25 mg once per day, or placebo | 7020 | 74 | 3.1 | Death from cardiovascular causes, non-fatal myocardial infarction (excluding silent myocardial infarction), or non-fatal stroke (0.86 (0.74 to 0.99)) | Doubling of serum creatinine with eGFR of ≤45 mL/min/1.73 m2, renal replacement therapy, or renal death (0.54 (0.40 to 0.75)) |
| Canagliflozin | CANVAS | Canagliflozin 100 mg once per day, with an optional increase to 300 mg once per day, or placebo | 10 142 | 76.5 | 2.4 | Death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke (0.86 (0.75 to 0.97)) | ≥40% reduction in eGFR, renal replacement therapy (transplant, chronic dialysis, or sustained eGFR<15 mL/min/1.73 m2), or renal death (0.53 (0.33 to 0.84)) |
| CREDENCE | Canagliflozin 100 mg once per day or placebo | 4401 | 56.2 | 2.62 | ESKD (dialysis, transplantation, or a sustained eGFR of <15 mL/min/1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes (0.70 (0.59 to 0.82)) | See primary composite outcome. | |
| Dapagliflozin | DECLARE-TIMI 58 | Dapagliflozin 10 mg once per day or placebo | 17 160 | 85.1 | 4.2 | Cardiovascular death, myocardial infarction, or ischemic stroke (0.93 (0.84 to 1.03)) | ≥40% reduction in eGFR to <60 mL/min/1.73 m2, ESKD (dialysis≥90 days, transplant or sustained eGFR 15 mL/min/1.73 m2), or renal or cardiovascular death (0.53 (0.43 to 0.66)) |
| DAPA-CKD | Dapagliflozin 10 mg once per day or placebo | 4304 | 43.1 | 2.4 | Sustained decline in the eGFR of at least 50%, ESKD, or death from renal or cardiovascular causes (0.61 (0.51 to 0.72)) | See primary composite outcome. | |
| Ertugliflozin | VERTIS CV | Ertugliflozin 5 mg once per day, ertugliflozin 15 mg once per day, or placebo | 8246 | 76.1 | 3.0 | Death from cardiovascular causes, non-fatal myocardial infarction, or non-fatal stroke (0.97 (0.85 to 1.11)) | Death from renal causes, renal replacement therapy, or doubling of the serum creatinine level (0.81 (0.63 to 1.04)) |
| Sotagliflozin | SCORED | Sotagliflozin 200 mg once per day, with an optional increase to 400 mg once per day, or placebo | 10 584 | 44.4 | 1.3 | Total number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits for heart failure (0.74 (0.63 to 0.88)) | Sustained decrease of ≥50% in the eGFR from baseline for ≥30 days, long-term dialysis, renal transplantation, or sustained eGFR of <15 mL/min/1.73 m2 for ≥30 days (0.71 (0.46 to 1.08)) |
CANVAS, Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes; CREDENCE, Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy; DAPA-CKD, Dapagliflozin in Patients with Chronic Kidney Disease; DECLARE-TIMI 58, Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes; eGFR, estimated glomerular filtration rate; EMPA-REG OUTCOME, Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes; ESKD, end-stage kidney disease; SCORED, Sotagliflozin in Patients with Diabetes and Chronic Kidney Disease; SGLT2i, sodium–glucose cotransporter-2 inhibitors; SGLT1/2i, combined sodium–glucose cotransporter-1 and -2 inhibitors; VERTIS CV, Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes.