Table 9.

Clinical studies of SGLT2 inhibitors.

Drug	Study Population	Treatment	Primary and Secondary Endpoints	Main Findings and Conclusions
Canagliflozin (CHIEF-HF trial) [133]	▪HF patients regardless of EF or diabetes status (N = 476).	Canagliflozin 100 mg OD or placebo for 12 weeks.	Primary: ▪Change in KCCQ TSS from baseline to week 12.	▪The 12-week change in KCCQ TSS was higher with canagliflozin. ▪Canagliflozin improved symptom burden in HF patients, regardless of EF or diabetes.
Dapagliflozin (DELIVER trial) [51]	▪Patients with LVEF ≥ 40% ▪With or without T2DM ▪Elevation of natriuretic peptide levels ▪Structural heart disease (N = 6232)	Dapagliflozin 10 mg OD or placebo	Primary: ▪A composite of worsening HF or CV death. Secondary: ▪Total number of worsening HF events and CV death. ▪Change in KCCQ TSS from baseline.	▪Total events and symptom burden were lower with dapagliflozin. ▪Dapagliflozin was associated with greater reductions in the combined risk of worsening HF or CV death in patients with mildly reduced or preserved EF.
Dapagliflozin (DAPA-HF trial) [134]	▪Patients with LVEF ≤ 40% and NYHA II–IV ▪NT-proBNP level ≥ 600 pg/mL ▪With or without T2DM (N = 4744)	Dapagliflozin 10 mg OD or placebo	Primary: ▪A composite of worsening HF or CV death Secondary: ▪A composite of hospitalization with HF or CV death. ▪Total number of CV death and hospitalizations for HF.	▪Dapagliflozin reduced the risk of worsening HF or death from CV causes, regardless of diabetes. ▪Dapagliflozin had better symptom scores. ▪No significant differences in the incidences of adverse events (e.g., hypoglycemia, volume depletion, and renal dysfunction).
Dapagliflozin (DEFINE-HF trial) [135]	▪Patients with LVEF ≤ 40% and NYHA II–III ▪Elevation of NT-proBNP or BNP level ▪eGFR ≥ 30 mL/min/1.73 m2 (N = 263)	Dapagliflozin 10 mg OD or placebo for 12 weeks	Primary: ▪Average of mean NT-proBNP at 6 and 12 weeks ▪A composite of the proportion of patients who achieved meaningful improvement in health status.	▪Dapagliflozin increased the proportion of patients experiencing clinically meaningful improvements in HF-related health status or natriuretic peptides. ▪No significant differences in the average 6- and 12-week NT-proBNP levels.
Empagliflozin (EMPEROR-Reduced trial) [136]	▪Patients with LVEF ≤ 40% and NYHA II–IV ▪Elevation of NT-proBNP level (N = 3730)	Empagliflozin 10 mg OD or placebo	Primary: ▪A composite of CV death or hospitalization with HF. Secondary: ▪Occurrence of all hospitalizations for HF. ▪Rate of decline of eGFR.	▪Empagliflozin had a lower total number of hospitalizations for HF compared with the placebo, regardless of diabetes status. ▪Empagliflozin had a slower rate of decline of eGFR and a lower risk of serious renal outcome. ▪Empagliflozin had a higher incidence of uncomplicated genital tract infection.
Empagliflozin (EMPEROR-Preserved trial) [137]	▪Patients with LVEF > 40% and NYHA II–IV ▪NT-proBNP > 300 pg/mL (N = 5988)	Empagliflozin 10 mg OD or placebo	Primary: ▪A composite of CV death or hospitalization with HF. Secondary: ▪Occurrence of all hospitalizations for HF.	▪Empagliflozin reduced the risk of CV death or hospitalization with HF, regardless of diabetes status. ▪Empagliflozin had a higher incidence of uncomplicated genital and urinary tract infections and hypotension.