Table 3.
Summary of SGLT2i CVOT results across the CV risk spectrum.
| Trials |
EMPA-REG OUTCOME [33,38,42,67] |
DECLARE-TIMI 58 [32] |
CANVAS-program [30,43] |
CREDENCE [31] |
|---|---|---|---|---|
| Intervention | Empagliflozin/placebo | Dapagliflozin/placebo | Canagliflozin/placebo | Canagliflozin/placebo |
| Primary outcomes | ||||
| 3-point MACE/Composite outcome (overall) | 0.86 (0.74–0.99) | 0.93 (0.84–1.03) | 0.86 (0.75–0.97) | 0.80 (0.67–0.95)a |
| eCVD | 0.86 (0.74–0.99) | 0.90 (0.79–1.02) | 0.82 (0.72–0.95) | 0.85 (0.69–1.06) |
| Multiple CVRF | NA | 1.01 (0.86–1.20) | 0.98 (0.74–1.30) | 0.68 (0.49–0.94) |
| Hx HF | NA | 1.01 (0.81–1.27) | 0.80 (0.61–1.05) | NA |
| No Hx HF | NA | 0.92 (0.82–1.02) | 0.87 (0.75–1.00) | NA |
| Key secondary outcomes | ||||
| CV death (overall) | 0.62 (0.49–0.77) | 0.98 (0.82–1.17) | 0.87 (0.72–1.06) | 0.78 (0.61–1.00) |
| eCVD | 0.62 (0.49–0.77) | 0.94 (0.76–1.18) | 0.86 (0.70–1.06) | 0.79 (0.58–1.07) |
| Multiple CVRF | NA | 1.06 (0.79–1.42) | 0.93 (0.60–1.43) | 0.75 (0.48–1.16) |
| Hx HF | 0.71 (0.43–1.16) | 1.01 (0.73–1.39) | 0.72 (0.51–1.02) | NA |
| No Hx HF | 0.60 (0.47–0.77) | 0.97 (0.78–1.20) | 0.95 (0.76–1.20) | NA |
| Fatal/nonfatal MI (overall) | 0.87 (0.70–1.09) | 0.89 (0.77–1.01) | 0.85 (0.69–1.05) | 0.86 (0.64–1.16) |
| eCVD | 0.87 (0.70–1.09) | 0.87 (0.74–1.02) | 0.79 (0.63–0.99) | 0.93 (0.66–1.32) |
| Multiple CVRF | NA | 0.94 (0.73–1.21) | 1.21 (0.73–2.00) | 0.70 (0.39–1.23) |
| Hx HF | NA | 0.85 (0.61–1.18) | 1.11 (0.65–1.89) | NA |
| No Hx HF | NA | 0.89 (0.77–1.04) | 0.86 (0.69–1.06) | NA |
| Fatal/nonfatal stroke (overall) | 1.18 (0.89–1.56) | 1.01 (0.84–1.21) | 0.90 (0.71–1.15) | 0.76 (0.55–1.22) |
| eCVD | 1.18 (0.89–1.56) | 0.97 (0.76–1.22) | 0.88 (0.67–1.16) | 0.87 (0.58–1.31) |
| Multiple CVRF | NA | 1.09 (0.82–1.45) | 0.97 (0.59–1.61) | 0.60 (0.34–1.08) |
| Hx HF | 1.48 (0.63–3.48) | 1.21 (0.77–1.91) | 0.84 (0.51–1.39) | NA |
| No Hx HF | 1.14 (0.85–1.53) | 0.98 (0.80–1.20) | 0.88 (0.68–1.14) | NA |
| HHF (overall) | 0.65 (0.50–0.85) | 0.73 (0.61–0.88) | 0.67 (0.52–0.87) | 0.61 (0.47–0.80) |
| eCVD | 0.65 (0.50–0.85) | 0.78 (0.63–0.97) | 0.68 (0.51–0.90) | 0.61 (0.44–0.85) |
| Multiple CVRF | NA | 0.64 (0.46–0.88) | 0.64 (0.35–1.15) | 0.61 (0.39–0.96) |
| Hx HF | 0.75 (0.48–1.19) | 0.73 (0.55–0.96) | 0.51 (0.33–0.78) | NA |
| No Hx HF | 0.59 (0.43–0.82) | 0.73 (0.58–0.92) | 0.79 (0.57–1.09) | NA |
| All-cause mortality (overall) | 0.68 (0.57–0.82) | 0.93 (0.82–1.04) | 0.87 (0.74–1.01) | 0.83 (0.68–1.02) |
| eCVD | 0.68 (0.57–0.82) | 0.92 (0.79–1.08) | 0.89 (0.75–1.07) | 0.79 (0.61–1.02) |
| Multiple CVRF | NA | 0.94 (0.78–1.12) | 0.79 (0.58–1.07) | 0.89 (0.63–1.26) |
| Hx HF | 0.79 (0.52–1.20) | 0.87 (0.68–1.12) | 0.70 (0.51–0.96) | NA |
| No Hx HF | 0.66 (0.51–0.81) | 0.94 (0.82–1.07) | 0.93 (0.78–1.11) | NA |
| Renal composite (overall) | 0.61 (0.53–0.70)b | 0.76 (0.67–0.87) | 0.60 (0.47–0.77) | 0.72 (0.54–0.97) |
| eCVD | NA | 0.79 (0.66–0.94) | 0.59 (0.44–0.79) | 0.83 (0.54–1.27) |
| Multiple CVRF | NA | 0.74 (0.60–0.91) | 0.63 (0.39–1.02) | 0.65 (0.43–0.97) |
| Hx HF | 0.78 (0.39–1.53) | 0.58 (0.36–0.92) | 0.67 (0.30–1.51) | NA |
| No Hx HF | 0.51 (0.37–0.70) | 0.52 (0.41–0.66) | 0.52 (0.37–0.72) | NA |
CI: confidence interval, CV: cardiovascular, CVD: cardiovascular disease, CVOTs: cardiovascular outcome trials, CVRF: cardiovascular risk factors, eCVD: established cardiovascular disease, eGFR: estimated glomerular filtration rate, HHF: hospitalization for heart failure, HR: hazard ratio, Hx HF: history of heart failure, MACE: major adverse cardiovascular events, MI: myocardial infarction, NA: not analyzed, No Hx HF: no history of heart failure, SGLT2i: sodium-glucose co-transporter 2 inhibitors, T2DM: type 2 diabetes mellitus.
All values presented as (HR [95% CI]). Values in bold represent overall population, and other values represent the respective subgroup population.
3-point MACE: composite of CV death, nonfatal MI, or nonfatal stroke.
Renal composite: CANVAS-program, % reduction in the eGFR, need for renal-replacement therapy, or death from renal causes, CREDENCE, dialysis, kidney transplantation, or renal death. DECARE-TIMI 58, ≥40% decrease in eGFR to <60 mL/min/1.73 m2, new end-stage renal disease, or death from renal or cardiovascular causes.
Primary outcome for CREDENCE, doubling of serum creatinine, end-stage kidney disease, renal death, or cardiovascular death.
Worsening nephropathy defined as new onset of UACR >300 mg/g creatinine or a doubling of the serum creatinine level and an estimated glomerular filtration rate of <45 mL/min/1.73 m2,the need for continuous renal-replacement therapy, or death from renal disease in EMPA-REG OUTCOME.