Table 1. Cardiovascular and renal outcomes in clinical trials with SGLT2 inhibitors.

CVOTs	EMPA-REG OUTCOME (8)	CANVAS (9)	DECLARE-TIMI 58 (10)	Meta-analysis of the three CVOTs (11)
				All patients	Patients with ASCVD	Patients without ASCVD
SGLT2 inhibitor	Empagliflozin, 10 or 25 mg	Canagliflozin, 100–300 mg	Dapagliflozin, 10 mg	Empagliflozin/canagliflozin/dapagliflozin
Follow-up (years)	3.1	3.6	4.2	≈3.7
Patients (n)	7,020	10,042	17,160	34,322	20,662	13,660
% patients with ASCVD (%)	>99	65.6	40.6	60.2	100	0
Primary endpoint MACE-3 points	0.86 (0.74–0.99), P=0.04	0.86 (0.75–0.97), P=0.02	0.93 (0.84–1.03), P=0.17	0.89 (0.83–0.96), P=0.0014	0.86 (0.80–0.93), P=0.0002	1.0 (0.87–1.16), P=0.98
Cardiovascular mortality plus hHF	0.66 (0.55–0.79), P=NT	0.78 (0.67–0.91), P=NT	0.83 (0.73–0.95), P=0.005	0.77 (0.71–0.84), P<0.0001**	0.76 (0.69–0.84), P<0.0001	0.84 (0.69–1.01), P=0.0634
Myocardial infarction	0.87 (0.70–1.09), P=0.23	0.85 (0.69–1.05), P=NT	0.89 (0.77–1.01), P=NT	0.89 (0.80–0.98), P=0.0177	0.85 (0.76–0.95), P=0.0045	0.99 (0.79–1.24), P=0.92
Stroke	1.18 (0.89–1.56), P=0.26	0.87 (0.69–1.09), P=NT	1.01 (0.84–1.21), P=NT	0.97 (0.86–1.10), P=0.64	0.98 (0.84–1.14), P=0.78	1.01 (0.80–1.28), P=0.94
hHF	0.65 (0.50–0.85), P=0.002	0.78 (0.67–0.91), P=NT*	0.73 (0.61–0.88), P=NT	0.69 (0.61–0.79), P<0.0001	0.71 (0.62–0.82), P<0.0001	0.64 (0.48–0.85), P=0.0021
Cardiovascular mortality	0.62 (0.49–0.77), P<0.001	0.87 (0.72–1.06), P=NT	0.98 (0.82–1.17), P=NT	0.84 (0.75–0.94), P=0.023	0.80 (0.71–0.91), P=0.0005	1.02 (0.80–1.30), P=0.89
All-cause mortality	0.68 (0.57–0.82), P<0.001	0.87 (0.74–1.01), P=0.24	0.93 (0.82–1.04), P=NT	0.85 (0.78–0.93), P=0.0002	0.83 (0.75–0.92), P=0.0003	0.90 (0.77–1.05), P=0.18
Progression of renal disease (composite endpoint)	0.61 (0.53–0.70), P<0.001	0.60 (0.47–0.77), P<0.001	0.53 (0.43–0.66), P=NT	0.55 (0.48–0.64), P<0.0001	0.56 (0.47–0.67), P<0.0001	0.54 (0.42–0.71), P<0.0001

Results are expressed as hazard ratio versus placebo (with 95% confidence interval). *, combined to cardiovascular mortality; **, with history of HF (11.3% of patients) (HR 0.61; 95% CI, 0.71–0.84; P<0.0001) versus without history of HF (HR 0.79; 95% CI, 0.71–0.88, P<0.0001). HR, hazard ratio; CI, confidence interval; ASCVD, atherosclerotic cardiovascular disease; CVOT, cardiovascular outcome trial; hHF, hospitalisation for heart failure; MACE-3 points, major cardiovascular events-3 points (cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke); NT, not tested because of prespecified hierarchical sequence.