Table 1.
Summary of SGLT-2i cardiovascular outcomes trials, including those in patients with HF (shown in italics)
| Trial name (date published) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| EMPA-REG OUTCOME (2015) [14] | CANVAS (2017) [10] | DECLARE–TIMI 58 (2019) [13] | VERTIS CV (2020) [18] | DAPA-HF (2019) [29] | EMPEROR-Reduced (2020) [32] | SOLOIST-WHF (2021) [34] | EMPEROR-Preserved (2021) [36] | ||||
| Focus of trial | CV outcomes | CV outcomes | CV outcomes | CV outcomes | HF outcomes | HF outcomes | HF outcomes | HF outcomes | |||
| Interventions |
Empagliflozin Placebo |
Canagliflozin Placebo |
Dapagliflozin Placebo |
Ertugliflozin Placebo |
Dapagliflozin Placebo |
Empagliflozin Placebo |
Sotagliflozin Placebo |
Empagliflozin Placebo |
|||
| Population | Patients with T2D and CVD (n = 7020) | Patients with T2D and with or at risk of CVD (n = 10,142) | Patients with T2D and with or at risk of CVD (n = 17,160) | Patients with T2D and CVD (n = 8246) | Patients with NYHA class II–IV HFrEF (n = 4744)a | Patients with NYHA class II–IV HFrEF (n = 3730)b | Patients with T2D, hospitalized for signs/symptoms of HF and treated with IV diuretic (n = 1222)c | Patients with NYHA class II–IV HFpEF (n = 5988)d | |||
| Median follow-up | 3.1 yrs | 126.1 wks | 4.2 yrs | 3.0 yrs | 18.2 months | 16 months | 9 monthse,f | 26.2 months | |||
| History of CVD, n (%) | 6964 (99.2) | 6656 (65.6) | 6974 (40.6) | 8246 (100) | 2674 (56.3)g | 1929 (51.2)g | NR | 2117 (35.4)g | |||
| History of HF, n (%) | 706 (10.1 | 1461 (10.4) | 1742 (10) | 1958 (23.7) | 4744 (100) | 3730 (100) | 1222 (100) | 5987 (100)h | |||
| Outcomes (HR, 95% CI)i | |||||||||||
| MACE | 0.86 (0.74–0.99) | 0.86 (0.75–0.97) | 0.93 (0.84–1.03) | 0.97 (0.85–1.11) | NR | NR | NR | NR | |||
| CV death/HHF | 0.65 (0.50–0.85) | 0.78 (0.67–0.91) | 0.83 (0.73–0.95) | 0.88 (0.75–1.03) | 0.75 (0.65–0.85) | 0.75 (0.65–0.86) | NR | 0.79 (0.69–0.90) | |||
| HHF | 0.65 (0.50–0.85) | 0.67 (0.52–0.87) | 0.73 (0.61–0.88) | 0.70 (0.54–0.90) | 0.70 (0.59–0.83) | 0.69 (0.59–0.81) | NR | 0.71 (0.60–0.83) | |||
| CV death | 0.62 (0.49–0.77) | 0.87 (0.72–1.06) | 0.98 (0.82–1.17) | 0.92 (0.77–1.11) | 0.82 (0.69– 0.98) | 0.92 (0.75–1.12) | 0.84 (0.58–1.22) | 0.91 (0.76–1.09) | |||
| Worsening HF/CV death | NR | NR | NR | NR | 0.74 (0.65–0.85) | NR | NR | NR | |||
| Deaths from CV causes, HHF, and urgent visits for HF | NR | NR | NR | NR | NR | NR | 0.67 (0.52–0.85) | NR | |||
| Deaths from CV causes, HHF, and urgent visits for HF/HF events during hospitalization | NR | NR | NR | NR | NR | NR | 0.68 (0.54–0.86) | NR | |||
| Death from CV causes/HHF/nonfatal MI/nonfatal strokes | NR | NR | NR | NR | NR | NR | 0.72 (0.56–0.92) | NR | |||
| HHF and urgent visits for HF | NR | NR | NR | NR | NR | NR | 0.64 (0.49–0.83) | NR | |||
CANVAS Canagliflozin Cardiovascular Assessment Study, CI confidence interval, CV cardiovascular, CVD cardiovascular disease, DAPA-HF Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure, DECLARE-TIMI 58 Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58, EMPA-REG OUTCOME Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients, EMPEROR-Preserved Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction, EMPEROR-Reduced Empagliflozin Outcome Trial in Patients with Chronic Heart Failure and a Reduced Ejection Fraction, HF heart failure, HFpEF heart failure with preserved ejection fraction, HFrEF heart failure with reduced ejection fraction, HHF hospitalization for heart failure, HR hazard ratio, IV intravenous, MACE major adverse cardiovascular events, MI myocardial infarction, NR not reported, NYHA New York Heart Association, SGLT-2i sodium-glucose cotransporter-2 inhibitor, SOLOIST-WHF Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure, T2D type 2 diabetes, VERTIS CV Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants with Vascular Disease
a41.8% of patients had T2D
b49.8% of patients had T2D
c79.1% of patients had left ventricular ejection fraction of < 50%
d49.1% of patients had T2D
e8.9 months in the placebo group and 9.2 months in the sotagliflozin group
fTrial enrolment was terminated early due to loss of funding from sponsor
gIschemic HF
hIschemic or nonischemic HF category not reported for one patient
iPrimary endpoint is shown in bold