Table 1.
Summary of major randomized trials exploring the effect of SGLT-2 inhibitors on cardiovascular and kidney failure outcomes.
| Parameter | Clinical Trial | |||||
|---|---|---|---|---|---|---|
| CV Outcome Trials | Kidney Failure Outcome Trials | |||||
| EMPA-REG OUTCOME | CANVAS | DECLARE-TIMI 58 | VERTIS | CREDENCE | DAPA-CKD | |
| Year | 2015 | 2017 | 2018 | 2020 | 2019 | 2020 |
| Patient characteristics | T2DM at high CV risk | T2DM at high CV risk | T2DM who had or were at high risk for atherosclerotic CV disease | T2DM and atherosclerotic CV disease | T2DM and albuminuric CKD | CKD with or without T2DM |
| N | 7020 | 10,142 | 17,160 | 8246 | 4401 | 4304 |
| SGLT-2 inhibitor | Empagliflozin | Canagliflozin | Dapagliflozin | Ertugliflozin | Canagliflozin | Dapagliflozin |
| Median follow-up (years) | 3.1 | 2.4 | 4.2 | 3.5 | 2.6 | 2.4 |
| eGFR (mL/min/1.73 m2) | 74 | 76 | 85 | 76 | 56 | 43 |
| eGFR < 60 mL/min/1.73 m2 (%) | 26 | 20 | 7 | 22 | 59 | 89 |
| UACR < 30 mg/g (%) | 60 | 70 | 69 | 58 | 0 | 0 |
| UACR 30–300 mg/g (%) | 29 | 22 | 24 | 30 | 0 | 10 |
| UACR > 300 mg/g (%) | 11 | 8 | 7 | 9 | 100 | 90 |
| Baseline ACEI or ARB use (%) | 81 | 80 | 81 | 81 | 99.9 | 98 |
| Primary outcome | CV death, non-fatal MI, or non-fatal stroke | CV death, non-fatal MI, or non-fatal stroke | CV death, non-fatal MI, or non-fatal stroke | CV death, non-fatal MI, or non-fatal stroke | Doubling of serum creatinine, ESKD or death from CV and renal causes | Sustained eGFR decline ≥50%, ESKD or death from CV and renal causes |
| HR * (95% CI) | 0.86 (0.74–0.99) | 0.86 (0.75–0.97) | 0.93 (0.84–1.03) | 0.97 (0.85–1.11) | 0.70(0.59–0.82) | 0.61 (0.51–0.72) |
Abbreviations: ACEI = angiotensin converting enzyme inhibitor; ARB = angiotensin receptor blocker; CI = confidence interval; CKD = chronic kidney disease; CV = cardiovascular; eGFR = estimated-glomerular-filtration-rate; ESKD = end-stage kidney disease; HR = hazard ratio; MI = myocardial infarction; SGLT-2 = sodium-glucose co-transporter type 2; T2DM = diabetes mellitus type 2; UACR = urinary albumin-to-creatinine ratio. * The EMPA-REG OUTCOME and CANVAS were designed as non-inferiority trials but showed superiority of empagliflozin and canagliflozin vs. placebo.