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Page 6 of 10 Min et al. Metab Target Organ Damage 2023;3:6 https://dx.doi.org/10.20517/mtod.2023.09

Table 2. Overview of Cardiovascular outcome trials of SGLT-2 inhibitors
Non-fatal Non-fatal All-cause
3P/4P- CV death
Inclusion Criteria Established MACE HR MI stroke mortality Other
HR
HR
CVD (%)
benefits
HR
HR (95%CI) (95%CI)
(95%CI) (95%CI) (95%CI)
EMPA-REG ●→ Age ≥ 18 years with 99% 0.86 (0.74- 0.62 (0.49- 0.87 (0.70- 1.24 (0.92- 0.68 (0.57- HHF
OUTCOME established CVD 0.99) P < 0.001; 0.77) 1.09) 1.67) 0.82) 0.65
[20 *
Empagliflozin P = 0.04 P < 0.001 P = 0.001 (0.50-
]
0.85)
Renal
benefits
CANVAS ●→ Age ≥ 30 years with 65% 0.86 (0.75- 0.87 (0.72- 0.85 (0.69- 0.90 (0.71- 0.87 (0.74- HHF
Canagliflozin [18] symptomatic ASCVD 0.97) 1.06) 1.05) 1.15) 1.01) 0.67
OR P < 0.001; P = (0.52-
●→ Age ≥ 50 years with 0.02 * 0.87)
≥ 2 CV risk factor Renal
outcome
0.60
(0.47-
0.77)
DECLARE ●→ Age ≥ 40 years with 41% 0.93 (0.84- 0.98 (0.82- 0.89 (0.77- 1.01 (0.84- 0.93 (0.82- HHF
TIMI-58 established CVD or ≥ 1 1.03) 1.17) 1.01) # 1.21) ^ 1.04) 0.73 (0.61-
[19]
Dapagliflozin CV risk factors 0.88)
Renal
outcome
0.53
(0.43-
0.66)
VERTIS-CV ●→Age ≥ 40 years with 100% 0.97 (0.85-1.11) 0.92 (0.77- 1.04 (0.86- 1.00 (0.76- 0.93 (0.80- HHF
[21]
Ertugliflozin ASCVD 1.11) 1.27) 1.32) 1.08) 0.70
(0.54-
0.90)
Renal
outcome
0.81 (0.63-
1.04)
*
CVD: Cardiovascular Disease; ASCVD: Atherosclerotic CVD; HHF: Hospitalisation for Heart Failure; CKD: Chronic Kidney Disease; P values are
# ^
for non-inferiority and superiority; Both fatal and non-fatal MI included; Both fatal and non-fatal stroke included.
Table 3. Overview of Heart Failure outcome trials of SGLT-2 inhibitors
P’ Composite HHF CV death All-cause
Study Inclusion Criteria T2D Outcome HR HR mortality Renal
(%) Benefit
HR (95%CI) (95%CI) (95%CI) HR (95%CI)
#
DAPA-HF ●→ Age ≥ 18 years with NYHA II- 42% 0.74 (0.65-0.85) P 0.70 (0.59- 0.82 (0.69- 0.83 (0.71-
Dapagliflozin [24] IV and EF ≤ 40% < 0.001 0.83) 0.98) 0.97)
(n = 4,744)
EMPORER- ●→ Age ≥ 18 years with NYHA II- 50% 0.75 (0.65-0.86) 0.70 (0.58- 0.91 (0.76- 1.00 (0.87-1.15) eGFR
##
Reduced IV and EF ≤ 40% P < 0.001 0.85) 1.09) decline
[26]
Empagliflozin (n = 3,730) 1.36 (1.06-
1.66)
P < 0.001
EMPORER- ●→ Age ≥ 40 years with 49% 0.79 (0.69-0.90) 0.73 (0.61- 0.91 (0.76- 1.00 (0.87-1.15) eGFR
#
Preserved established CVD or ≥ 1 CV risk P < 0.001 0.88) 1.09) decline
Empagliflozin [27] factors 1.36 (1.06-
(n = 5,988) 1.66)
P < 0.001
##
DELIVER ●→ Age ≥ 40 years with ASCVD 48% 0.82 (0.73-0.92) 0.79 (0.69- 0.88 (0.74- 0.94 (0.83-
[25]
Dapagliflozin (n = 6,263) P < 0.001 0.91) 1.05) 1.07)
#
##
HHF: Hospitalisation for Heart Failure; CKD: Chronic Kidney Disease; Primary composite outcomes: worsening HF or CV death; Primary
composite outcomes: HHF or CV death