Table 1.

Main preclinical studies testing the effects of SGLT2 inhibitors on cardiac function.

Year	First Author	SGLT2 inhibitor(s) tested	Main conclusions	Novel Information	Reference
2017	Byrne	Empagliflozin	Empagliflozin decreased worsening of cardiac function in a mouse model of pressure overload-induced HF.	SGLT2 inhibition prevents the progressive decline of cardiac function even in non-diabetic murine models with reduced EF both in vivo and ex vivo.	[7]
2017	Andreadou	Empagliflozin	Empagliflozin improved myocardial function, reduced infarct size, decreased iNOS expression and lipid peroxidation in mice.	Identification of the anti-oxidant and anti-inflammatory properties of empagliflozin mediated by the activation of STAT3 pathway.	[8]
2017	Lee	Dapagliflozin	Dapagliflozin reduced myofibroblast infiltration during postinfarction remodeling in infarcted rat hearts.	Demonstration of the regulation of macrophage polarization via STAT3 by dapagliflozin.	[14]
2018	Aroor	Empagliflozin	Empagliflozin improved kidney injury causing glycosuria and reducing systemic and renal artery stiffness in a mouse model of T2DM.	SGLT2 inhibition enhances eNOS activation and mitigates the hyperglycemia-induced suppression of the antifibrotic factor RECK in the kidney.	[10]
2019	Shao	Empagliflozin	Empagliflozin reduced the remodeling of atrial structural and electrical conformation reducing left atrial diameter, interstitial fibrosis.	Demonstration of the beneficial effects of empagliflozin on atrial fibrillation in diabetic rats.	[9]
2020	Lahwong	Dapagliflozin	Dapagliflozin administration in acute setting reduced cardiac infarct size, increased LV function and reduced rate of arrhythmias in rats with I/R injury.	Evidence of the direct effects of dapagliflozin on cardiac apoptosis, inflammation, ionic homeostasis, and oxidative stress pathways.	[13]
2021	Quagliariello	Empagliflozin	Empagliflozin reduced doxorubicin toxic effects on cardiomyocytes.	Identification of new anti-inflammatory and cardioprotective mechanisms of empagliflozin involving NLRP3 and MyD88-related pathways.	[11]
2021	Sayour	Canagliflozin, Dapagliflozin, Empagliflozin	SGLT2 inhibitors reduced myocardial infarct size in animal models independent of diabetes.	The reduction of infarct size is equal for the different types of SGLT2 inhibitors, suggesting a class effect.	[65]
2023	Chen	Empagliflozin	Empagliflozin (10 mg/kg/day) has protective effects in a model of cardiac ischemia/reperfusion despite the ablation of SGLT2 (global knock-out mouse).	The demonstration of the beneficial heart effects of SGLT2 inhibitors in a SGLT2 KO mouse model suggests that the reduction of the infarct size is not directly mediated by the SGLT2 protein.	[95]

EF: Ejection Fraction; I/R: Ischemia/Reperfusion; HF: Heart Failure; HFD + STZ: high-fat diet /streptozotocin; KO: Knock-Out; LV: Left Ventricular; SGLT2: Sodium–glucose cotransporter 2; T2DM: Type 2 Diabetes Mellitus.