Table 1.
Main clinical trials evaluating cardiovascular outcomes among patients treated with SGLT2-Is.
| Drug | Trial (Ref.) |
Patients | Follow-Up (Median) |
Outcomes | Hazard Ratio (95% CI) |
|---|---|---|---|---|---|
| Empagliflozin | EMPAREG OUTCOME study [47] | 7020 T2DM patients at high risk for CV events and an eGFR ≥ 30 mL/min/1.73 m2 |
3.1 years (2.6 years of treatment) |
composite of death from CV causes, nonfatal myocardial infarction, or nonfatal stroke | 0.86 (0.74–0.99) |
| empagliflozin 10 mg vs. empagliflozin 25 mg vs. matching placebo |
death from cardiovascular causes
nonfatal myocardial infarction nonfatal stroke |
0.62 (0.49–0.77) 0.87 (0.70–1.09) 1.24 (0.92–1.56) |
|||
| hospitalization for heart failure | 0.65 (0.50–0.85) | ||||
| death from any cause | 0.68 (0.57–0.82) | ||||
| EMPEROR-Reduced [101] | 3730 diabetic or not diabetic patients with class II, III, or IV HF and EF ≤ 40% | 16 months | cardiovascular death or hospitalization for worsening heart failure | 0.75 (0.65–0.86) | |
| empagliflozin 10 mg vs. placebo (in addition to recommended therapy) |
hospitalization for heart failure | 0.70 (0.58–0.85) | |||
| EMPEROR-Preserved [114] | 26.2 months | cardiovascular death or hospitalization for worsening heart failure | 0.79 (0.69–0.90) | ||
| 5988 diabetic or not diabetic patients with class II-IV HF and EF > 40% | hospitalization for heart failure | 0.73 (0.61–0.88) | |||
| empagliflozin 10 mg vs. placebo (in addition to usual therapy) |
|||||
| EMPERIAL [104] | 12 weeks | change in 6-minute walk test distance | ns | ||
| patients with HFrE (EF ≤ 40%, n = 312) or with HFpEF (EF > 40%, n = 315) | KCCQ-TSS (Kansas City Cardiomyopathy Questionnaire Total Symptom Score) | ns | |||
| empagliflozin 10 mg vs. placebo | CHQ-SAS (Chronic Heart Failure Questionnaire Self-Administered Standardized format) dyspnoea score | ns | |||
| Canagliflozin | CANVAS study [46] |
10,142 participants with T2DM and high CV risk 100 mg (with an optional increase to 300 mg) vs. placebo |
188.2 weeks | composite of death from CV causes, nonfatal myocardial infarction, or nonfatal stroke | 0.86 (0.75–0.97) |
| Dapagliflozin | DECLARE-TIMI 58 [48] | 17,160 T2DM patients at high risk for CV events (only 7% of patients had an eGFR < 60 mL/min/1.73 m2) | 4.2 years | composite of CV death, myocardial infarction, or ischemic stroke | 0.93 (0.84–1.03) |
| dapagliflozin 10 mg vs. placebo | CV death or hospitalization for HF | 0.83 (0.73–0.95) | |||
| hospitalization for HF | 0.73 (0.61–0.88) | ||||
| DAPA-HF Trial [100] | 4304 diabetic (68%) or not diabetic patients with class II-IV HF | 18.2 months | worsening HF (hospitalization or urgent visit resulting in IV therapy for HF) or CV death | 0.74 (0.65–0.85) | |
| dapagliflozin 10 mg vs. placebo | first worsening HF event | 0.70 (0.59–0.83) | |||
| (in addition to recommended therapy) | CV death | 0.83 (0.71–0.97) | |||
| DEFINE HF [103] | 263 diabetic or not diabetic patient with class II-III HF | 12 weeks | mean NT-proBNP | ns | |
| dapagliflozin 10 mg vs. placebo | % of patients with ameliorated functional status | 1.8 (1.03–3.06) | |||
| Sotagliflozin | SCORED [93] |
10,584 T2DM patients with CKD and CV risk sotagliflozin 200–400 mg vs. placebo |
16 months | composite of CV death, hospitalization fo HF, and urgent visit for HF | 0.74 (0.63–0.88) |
| SOLOIST-WHF [102] |
1222 T2DM patients recently hospitalized for worsening HF sotagliflozin 200–400 mg vs. placebo |
9 months | CV deaths and hospitalization or urgent visits for HF | 0.67 (0.52–0.85) | |
| CV death | 0.84 (0.58–1.22) | ||||
| death from any cause | 0.82 (0.59–1.14) | ||||
| Ertugliflozin | VERTIS CV study [92] | 8246 T2DM patients with established CV disease and an eGFR ≥ 30 mL/min/ 1.73 m2 | 3 years | composite of CV death, myocardial infarction, or ischemic stroke | 0.97 (0.85–1.11) |
| ertugliflozin 5 or 15 mg vs. placebo | death from CV causes or hospitalization for HF | 0.88 (0.75–1.03) | |||
| death from CV causes | 0.92 (0.77–1.11) |