Sodium glucose cotransporter-2 inhibitors and heart disease: Current perspectives

Table 1 Major cardiovascular outcome trials of sodium glucose cotransporter 2 inhibitors

	EMPA-REG outcome		CANVAS	DECLARE-TIMI 58	VERTIS-CV	SCORED
Intervention	Empagliflozin 10 and 25 mg vs placebo		Canagliflozin 100 and 300 mg vs placebo	Dapagliflozin 10 mg vs placebo	Ertugliflozin 5 and 15 mg vs placebo	Sotagliflozin vs placebo
Population	n = 7020, T2DM with established CV disease		n = 10142 patients, T2DM with established CV disease or ≥ 2 CV risk factors	n = 17160 patients, T2DM with established CV disease or risk factors for atherosclerotic CV disease	n = 8246, T2DM with established CV disease	10584 patients with T2DM and established CV disease or risk factors for atherosclerotic CV disease
Established CV disease (%)	99		66	41	99	48.6
Follow up period (yr)	3.1		3.6	4.2	3.5	1.3
HbA1c (%) at baseline	7.0% to 10.0% (for those on a stable background therapy); 7.0%-9.0% (for medication-naive patients)		7.0% to 10.5%	6.5% to 12.0%	7.0% to 10.5%	> 7%
Estimated GFR	≥ 30		≥ 30	≥ 60	≥ 30	25-60
Primary outcome, HR (95%CI)	3P-MACE, 0.86 (0.74-0.99)		3P-MACE, 0.86 (0.75-0.97)	3P-MACE, 0.93 (0.84-1.03); CV death or hospitalization for HF, 0.83 (0.73-0.95)	3P-MACE, 0.97 (0.85-1.11)	Total no. of deaths from cardiovascular causes, hospitalizations for HF, and urgent visits for HF 0.74 (0.63-0.88)
Key secondary outcome (s), HR (95%CI)	4P-MACE, 0.89 (0.78-1.01)		All-cause mortality (as below); CV death (as below); progression of albuminuria, 0.73 (0.67-0.79); CV death or hospitalization for HF 0.78 (0.67-0.91)	≥ 40% decline in eGFR to < 60 mL/min/1.73 m2 or new onset end-stage renal disease or renal/CV mortality, 0.76 (0.67-0.87); all-cause mortality (as below)	CV death or hospitalization for HF, 0.88 (0.75-1.03); CV death (as below); renal death or dialysis/transplant or doubling of serum creatinine from baseline, 0.81 (0.63-1.04)	Total No. or hospitalizations for HF and urgent visits for HF HR: 0.67 (0.55-0.82); deaths from cardiovascular causes (as below)
Other secondary outcomes
CV death, HR (95%CI)		0.62 (0.49-0.77)	0.87 (0.72-1.06)	0.98 (0.82-1.17)	0.92 (0.77-1.11)	0.90 (0.73-1.12)
All-cause mortality, HR (95%CI)		0.68 (0.57-0.82)	0.87 (0.74-1.01)	0.93 (0.82-1.04)	0.93 (0.80-1.08)	0.99 (0.83-1.18)
Fatal or non-fatal myocardial Infarction, HR (95%CI)		0.87 (0.70-1.09)	0.89 (0.73-1.09)	0.89 (0.77 − 1.01)	1.04 (0.86-1.26)	0.68 (0.52-0.89)
Fatal or non-fatal stroke, HR (95%CI)		1.18 (0.89-1.56)	0.87 (0.69-1.09)	1.01 (0.84-1.21)	1.06 (0.82-1.37)	0.66 (0.48-0.91)
Hospitalization for HF, HR (95%CI)		0.65 (0.50-0.85)	0.67 (0.52-0.87)	0.73 (0.61-0.88)	0.70 (0.54-0.90)	0.67 (0.55-0.82)

EMPA-REG outcome: Empagliflozin and canagliflozin in the empagliflozin cardiovascular outcome; event trial in type 2 diabetes mellitus patients; CANVAS: Canagliflozin cardiovascular assessment study; DECLARE-TIMI 58: Dapagliflozin effect on cardiovascular events-thrombolysis in myocardial infarction 58; T2DM: Type 2 diabetes mellitus; CV: Cardiovascular; GFR: Glomerular filtration rate; HR: Hazard ratio; 3P-MACE: 3 point - major adverse CV event; HF: Heart failure; eGFR: Estimated glomerular filtration rate.