Table 1.

Large clinical trials of SGLT2 inhibitors.

Drug	Trial	Patients	Median observation time	Primary outcome, [HR (95% CI), P-value]
Empagliflozin	EMPA-REG (18)	7,020 T2DM patients with CVD and Egfr ≥30 mL/min/1.73 m2	3.1 years	MACEa,0.86 (0.74–0.99), P = 0.04
	EMPEROR-Reduced (19)	3,730 patients with HFrEF	16 months	CVD death or hospitalization for HF, 0.75 (0.65–0.86), P < 0.001
	EMPEROR-Preserved (20)	5,988 HF patients with EF > 40%	26.2 months	CVD death or hospitalization for HF, 0.79 (0.69–0.90), P < 0.001
Canagliflozin	CREDENCE (21)	4,401 patients with T2DM and CKDb	2.62 years	ESKDc, a doubling of the serum creatinine level, or death from renal or CVD, 0.70 (0.59–0.82), P < 0.001
	CANVAS (22)	10,142 T2DM patients with CVD risk factors, eGFR≥30 mL/min/1.73 m2	126.1 weeks	MACEd,0.86 (0.75–0.97), P = 0.02
Dapagliflozin	DECLARE-TIMI (23)	17,160 T2DM patients with ASCVD or CVD risk factor	4.2 years	MACEe,0.93 (0.84–1.03), P = 0.17
	DAPA-HF (24)	4,744 patients with HFrEF, NT-proBNP≥600 pg/mL	18.2 months	Worsening HFf or CVD death, 0.74 (0.65–0.85), P < 0.001
	DAPA-CKD (25)	4,304 patients with eGFR 25 to 75 mL/min/1.73 m2and UACR 200 to 5,000 mg/g	2.4 years	A sustained decline in the eGFR of at least 50%, ESKDg, or death from renal or CVD causes, 0.61 (0.51–0.72), P < 0.001
Ertugliflozin	VERTIS-CV (26)	8,246 T2DM patients with ASCVD and eGFR≥30 mL/min/1.73 m2	3.5 years	MACEh, 0.97 (0.85–1.11), P < 0.001 for non-inferiority
Sotagliflozin	SOLOIST-WHF (27)	1,222 T2DM patients were hospitalized due to the presence of signs and symptoms of HF and were treated with intravenous diuretic therapy and eGFR≥30 mL/min/1.73 m2	9.0 months	The first occurrence of CVD-related death causes or hospitalization for HF 0.67 (0.52–0.85), P < 0.001
	SCORED (28)	10,584 T2DM patients with eGFR of 25 to 60 mL/min/1.73 m2 and risk factors for cardiovascular disease	16 months	MACEi,0.74 (0.63–0.88), P < 0.001

^a Death from CVD causes, non-fatal MI, or non-fatal stroke;

^b eGFR of 30 to <90 mL/min/1.73 m² of body-surface area and albuminuria (UACR, >300 to 5,000, with albumin measured in milligrams and creatinine in grams);

^c Dialysis, transplantation, or a sustained eGFR of < 15 mL/min/1.73 m²;

^d Death from CVD causes, non-fatal MI, or non-fatal stroke;

^e CVD death, MI, or ischemic stroke;

^f Hospitalization or an urgent visit resulting in intravenous therapy for HF;

^g Maintenance dialysis for ≥28 days, kidney transplantation, or an eGFR of <15 mL/min/1.73 m² confirmed by a second measurement after ≥28 days;

^h Death from CVD causes, non-fatal MI, or non-fatal stroke;

ⁱDeath from CVD causes, non-fatal myocardial infarction, or non-fatal stroke.

ASCVD, Atherosclerotic cardiovascular disease; CI, Confidence interval; CKD, Chronic kidney disease; CVD, Cardiovascular disease; EF, Ejection fraction; eGFR, Estimated glomerular filtration rate; ESKD End stage kidney disease; HFrEF, Heart failure with reduced ejection fraction; HR, Hazard ratio; MACE, Major adverse cardiac events; MI, Myocardial infarction; NT-proBNP, N-terminal pro-brain natriuretic peptide; T2DM, Type 2 Diabetes Mellitus; UACR, Urinary albumin-to-creatinine ratio.