Antidiabetic combination therapy and cardiovascular outcomes: An evidence-based approach

Table 2 Data from major cardiovascular outcome trials with sodium-glucose co-transporter 2 inhibitor

Trial name (n)	Drug vs comparator	Baseline CVD or risk factors (%)	Mean difference in HbA1c (%) (95%CI)	Mean difference in body weight in kg (95%CI)	Primary outcome HR (95%CI)	Hospitalization for heart failure HR (95%CI)	Composite CV death or heart failure hospitalization HR (95%CI)
CANVAS (n = 10142)[31]	Canagliflozin vs placebo	ASCVD (66); CAD (56); Stroke/CVD (19); HF (14.4)	-0.58 (-0.61 to -0.56)	-1.6 (-1.70 to -1.51)	3-point MACE: 0.86 (0.75 to 0.97); P < 0.001 for non-inferior; P = 0.02 for superior	0.67 (0.52 to 0.87)	0.78 (0.67 to 0.91). Amputation risk at the toe and metatarsal level
DECLARE-TIMI (n = 17160)[32,33]	Dapagliflozin vs placebo	ASCVD (41); CAD (33); Prior MI (21); Stroke/CVD (7); HF (10)	-0.42 (-0.45 to -0.40)	-1.80 (-2.00 to -1.70)	3-point MACE: 0.93 (0.84-1.03); P < 0.001 for-non-inferior and P = 0.17 for superior	0.73 (0.61 to 0.88); P < 0.005	0.83 (0.73 to 0.95); P = 0.005 for superiority
EMPA-REG (n = 7020)[30]	Empagliflozin vs placebo	ASCVD (99); CAD (76); Prior MI (46); Stroke (23); HF (10)	-0.57 ( -0.70 to -0.43) for 10 mg	-1.63 (-2.11 to -1.5) for 10 mg	3-point MACE: 0.86 (0.74 to 0.99); P < 0.001 for non-inferior and 0.04 for superior	0.65 (0.5 to 0.85); P = 0.002	0.62 (0.49 to 0.77); P < 0.001
			-0.64 (-0.77 to -0.50) for 25 mg	-2.01 ( -2.49 to -1.53) for 25 mg
VERTIS-CV (n = 8246)[34]	Ertugliflozin vs placebo	ASCVD (100); CAD (76); Prior MI (48); Stroke/CVD (23); HF (24)	-0.70 (-0.90 to -0.50) for 5 mg	-3.00 (-3.30 to -2.70) for 5 mg	3-point MACE: 0.97 (0.85 to 1.11); P < 0.001 for noninferior	0.7 (0.54 to 0.9)	0.88 (0.75 to 1.03); P = 0.11 for superiority
			-0.90 (-1.00 to -0.70) for 15 mg	-2.90 (-3.20 to -2.60) for 15 mg
SCORED (n = 10584)[35]	Sotaglifozin vs placebo	ASCVD (89); Prior MI (19.9); Prior PCI (22.8); HF (31); Stroke (8.9)	-1.16 (-1.26 to -1.06)	-1.16 (-1.26 to -1.06)	Total number of deaths from CV causes, hospitalization for HF, and urgent visits for HF: 0.74 (0.63-0.88); P < 0.001	0.67 (0.55 to 0.82); P < 0.001	0.77 (0.66 to 0.91)

CVD: Cardiovascular disease; HbA1c: Glycated hemoglobin; CV: Cardiovascular; HR: Hazard ratio; CI: Confidence interval; ASCVD: Atherosclerotic cardiovascular disease; CAD: Coronary artery disease; HF: Heart failure; MACE: Major adverse cardiovascular events; MI: Myocardial infarction; PCI: Percutaneous coronary intervention.