Table 1.
Characteristics of the trials included in the meta-analysis
| EMPA-REG | CANVAS | DECLARE-TIMI 58 | CREDENCE | VERTIS-CV | |
|---|---|---|---|---|---|
| National clinical trial number | NCT01131676 | NCT01730534 | NCT02065791 | NCT01986881 | |
| Drug | Empagliflozin | Canagliflozin | Dapagliflozin | Canagliflozin | Ertugliflozin |
| Comparator | Placebo | Placebo | Placebo | Placebo | Placebo |
| Study participants | 7020 | 10,142 | 17,160 | 4401 | 8246 |
| Duration, years | 3.1 | 3.6 | 4.2 | 2.62 | 3.5 |
| Outcome of interest | Primary endpoint: cardiovascular death, myocardial infarction, stroke | Primary endpoint: cardiovascular death, myocardial infarction, stroke | Primary endpoint: cardiovascular death, myocardial infarction, stroke | Secondary endpoint: cardiovascular death, myocardial infarction, or stroke | Primary endpoint: cardiovascular death, myocardial infarction, or stroke |
| Patients’ characteristics | |||||
| Age, years | 63.2 ± 8.8 | 63.2 ± 8.3 | 63.9 ± 6.8 | 63 ± 9.2 | 64.4 ± 8.1 |
| Gender (male), % | 72.0 | 64.9 | 62.6 | 66.1 | 69.9 |
| Diabetes duration, years | N/A | 13.5 ± 7.7 | 11 (6–16) | 15.8 ± 8.6 | 13 ± 8.3 |
| Baseline glycated hemoglobin, % | 8.1 ± 0.8 | 8.2 ± 0.9 | 8.3 ± 1.2 | 8.3 ± 1.3 | 8.2 ± 1.1 |
| Baseline body mass index, kg/m2 | 30.7 ± 5.2 | 31.9 ± 5.9 | 32.1 ± 6.0 | 31.3 ± 6.2 | 31.9 ± 5.4 |
| Systolic blood pressure, mmHg | 136 ± 17 | 136 ± 16 | 135 ± 15 | 140 ± 15.6 | 113 ± 14 |
| Diastolic blood pressure, mmHg | 77 ± 10 | 78 ± 10 | 85 ± 16 | 78 ± 9 | 77 ± 8 |
| History of cardiovascular disease, % | 99.0 | 72.2 | 40.6 | 50.4 | 100.0 |
| Heart failure, % | 10.5 | 14.4 | 10.0 | 29.4 | 23.7 |
| Estimated glomerular filtration rate < 60 ml/min/1.73 m2, % | 25.9 | 20.1 | 7.4 | 59.8 | 21.9 |
| Diabetes, % | 100 | 100 | 100 | 100 | 100 |
| SOLOIST | DAPA-HF | DAPA-CKD | |
|---|---|---|---|
| National clinical trial number | NCT03521934 | NCT03036124 | NCT03036150 |
| Drug | Sotagliflozin | Dapagliflozin | Dapagliflozin |
| Comparator | Placebo | Placebo | Placebo |
| Study participants | 1222 | 4744 | 4304 |
| Duration, years | 0.8 | 1.5 | 2.4 |
| Outcome of interest | Primary endpoint: cardiovascular death, hospitalization for heart failure, urgent heart failure visits | Primary endpoint: cardiovascular death, hospitalization for heart failure, urgent heart failure visits | Primary endpoint: a decline of at least 50% in the estimated GFR, onset of end-stage kidney disease |
| Patients’ characteristics | |||
| Age, years | 70 (63–76) | 66.2 ± 10.9 | 61.9 ± 12.1 |
| Gender (male), % | 66.2 | 76.6 | 66.9 |
| Diabetes duration, years | N/A | N/A | N/A |
| Baseline glycated hemoglobin, % | 7.2 (6.4–8.3) | N/A | N/A |
| Baseline body mass index, kg/m2 | 31.1 (26.3–34.5) | 28.2 ± 6.0 | 29.5 ± 6.2 |
| Systolic blood pressure, mmHg | 122 (111–135) | 122 ± 16 | 137 ± 17 |
| Diastolic blood pressure, mmHg | 73 (66–80) | N/A | 78 ± 11 |
| History of cardiovascular disease, % | N/A | N/A | 37.4 |
| Heart failure, % | 100.0 | 100.0 | 10.9 |
| Estimated glomerular filtration rate < 60 ml/min/1.73 m2, % | 69.8 | 40.6 | 90.0 |
| Diabetes, % | 100.0 | 45.0 | 67.5 |
Variables are expressed as mean ± standard deviation or median (interquartile range), unless percentages are shown
EMPA-REG (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients, CANVAS Canagliflozin Cardiovascular Assessment Study, CREDENCE Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation, DECLARE-TIMI 58, Multicenter Trial to Evaluate the Effect of Dapagliflozin on the Incidence of Cardiovascular Events, N/A not applicable, VERTIS-CV Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial, SOLOIST-WHF Effect of Sotagliflozin on Cardiovascular Events in Patients with Type 2 Diabetes Post Worsening Heart Failure, DAPA-HF Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients with Chronic Heart Failure, DAPA-CKD A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease, N/A not applicable