Table 2.
Summary of Clinical Trials Studying SGLT2 Inhibitors in Cardiovascular and Renal Outcomes
| DECLARE-TIMI 58 | EMPA-REG OUTCOME | CANVAS Program | CREDENCE | |
|---|---|---|---|---|
| Intervention | Dapagliflozin | Empagliflozin | Canagliflozin | Canagliflozin |
| Dose | 10 mg | 10 mg, 25 mg | 100 mg, 300 mg | 100 mg |
| Number of participants | 17,160 | 7020 | 10,142 | 4401 |
| Mean age (years) | 63.9 | 63.1 | 63.3 | 63 |
| Follow up (years) | 4.2 | 3.1 | 2.4 | 2.6 |
| Established CV disease (%) | 41 | 41 | 66 | 99 |
| RAAS inhibitors (%) | 81.3 | 81 | 80.2 | 99.9 |
| eGFR inclusion criteria | CrCl≥60 mL/min (Cockcroft-Gault) | ≥30 (MDRD) | ≥30 (MDRD) | 30–90 (CKD-EPI) |
| Baseline eGFR (mL/min/1.73m2) ≥90 60–90 45–60 <45 |
8162 (47.6%) 7732 (45.1%) 1265 (7.4%) 554 (5.5%) |
1538 (21.9%) 3661 (52.2%) 1249 (17.8%) 570 (8.1%) |
2476 (24.4%) 5625 (55.5%) 1485 (14.6%) 554 (5.5%) |
0 1809 (41%) 1279 (29.1%) 1313 (29.8%) |
| UACR criteria (mg/g) | None | None | None | >300–5000 |
| Baseline UACR subgroup (mg/g) <30 30–300 >300 |
11,644 (67.9%) 4030 (23.5%) 1169 (6.8%) |
4171 (59.4%) 2013 (28.7%) 769 (11%) |
7007 (69.1%) 2266 (22.3%) 760 (7.5%) |
0 0 4401 (100%) |
| Primary outcome (HR [95% CI]) |
3-point MACE 0.93 (0.84–1.03) |
3-point MACE 0.86 (0.74–0.99) |
3-point MACE 0.86 (0.75–0.97) |
Primary composite Kidney and CV outcome* 0.70 (0.59–0.82) |
| Sec. outcomes (HR [95% CI]) CV death MI Stroke Hospitalization HF |
0.98 (0.82–1.17) 0.89 (0.77–1.01) 1.01 (0.84–1.21) 0.73 (0.61–0.88) |
0.62 (0.49–0.77) 0.87 (0.70–1.09) 1.18 (0.89–1.56) 0.65 (0.50–0.85) |
0.87 (0.72–1.06) 0.89 (0.73–1.09) 0.87 (0.69–1.09) 0.67 (0.52–0.87) |
0.69 (0.57–0.83) 0.80 (0.67–0.95)** 0.61 (0.47–0.80) |
| All-cause mortality (HR [95% CI]) |
0.93 (0.82–1.04) | 0.68 (0.57–0.82) | 0.87 (0.74–1.01) | 0.83 (0.68–1.02) |
Notes: *ESRD (dialysis, transplantation, or sustained eGFR < 15 mL/min/1.73 m2), doubling of the serum creatinine, or death from renal or CV causes. **CV death, MI or stroke: 38.7 vs 48.7/1000 P-Y (HR 0.80; 95% CI 0.67–0.95; P=0.01), NNT=40 (23–165).
Abbreviations: CV, cardiovascular; RAAS, renin-angiotensin-aldosterone system; eGFR, estimated glomerular filtration rate; UACR, urine albumin-creatinine ratio; HR, hazard ratio; MI, myocardial infarction; HF, heart failure; CI, confidence interval.