Sodium-glucose cotransporter 2 inhibitors’ mechanisms of action in heart failure

Table 1 Major cardiovascular outcome trials with sodium-glucose cotransporter 2 inhibitors

Parameters	EMPA-REG OUTCOME	CANVAS program	DECLARE-TIMI 58
Intervention	Empagliflozin/placebo	Canagliflozin/placebo	Dapagliflozin/placebo
Median follow-up (yr)	3.1	3.6	4.2
Number of patients	7020	10142	17160
Prior cardiovascular disease/heart failure (%)	99/10	65.6/14.4	40/10
Primary outcome (3-point MACE)	0.86 (95%CI: 0.74-0.99) Noninferiority, P < 0.001; Superiority, P = 0.04	0.86 (95%CI: 0.75-0.97) Noninferiority, P < 0.001; Superiority, P = 0.02	0.93 (95%CI: 0.84-1.03) Noninferiority, P < 0.001; Superiority, P = 0.17
Cardiovascular death	0.62 (0.49-0.77)1	0.87 (0.72-1.06)	0.98 (0.81-1.17)
Myocardial infarction	0.87 (0.70-1.09)	0.89 (0.73-1.09)	0.89 (0.77-1.01)
Stroke	1.18 (0.89-1.56)	0.87 (0.69-1.09)	1.01 (0.84-1.21)
Heart failure hospitalization	0.65 (0.50-0.85)1	0.67 (0.52-0.87)1	0.73 (0.61-0.88)1
All cause mortality	0.68 (0.57-0.82)1	0.87 (0.74-1.01)	0.93 (0.82-1.04)

MACE: Major adverse cardiac event.

¹Significant.

Table 2 Ongoing larger clinical trials of sodium-glucose cotransporter 2 inhibitors in heart failure

Trial	Drug	Ejection fraction	Diabetic/nondiabetic
Emperor-reduced	empagliflozin	HFrEF	Both
Emperor-preserved	empagliflozin	HFpEF	Both
Deliver	dapagliflozin	HFpEF	Both

HFrEF: Heart failure with reduced ejection fraction; HFpEF: Heart failure with preserved ejection fraction.