Table 1.

Clinical, Cellular, and Molecular Features That Distinguish Hemodynamically Active Drugs, Established Neurohormonal Antagonists, and SGLT2 Inhibitors

	Diuretics, Systemic Vasodilators, and Positive Inotropic Drugs	Established Neurohormonal Antagonists	SGLT2 Inhibitors
Immediate effects on cardiac output, filling pressures, and natriuretic peptides	Present and desirable	Often absent and frequently undesirable	Generally absent in clinically stable patients
Ability to rapidly improve symptoms, exercise tolerance, and quality of life	Frequently present	Frequently absent	Generally absent
Effect to reduce the risk of cardiovascular death	Usually absent	Characteristically present	Usually present
Effect to ameliorate oxidative stress, organellar dysfunction, and cellular inflammation	Usually absent	Characteristically present	Characteristically present
Enhancement of SIRT1/AMPK and attenuation of Akt/mTOR signaling	Inconsistent and not characteristic	Present with several drug classes	Characteristic of members of the drug class
Augmentation of autophagic flux	Inconsistent and not characteristic	Reported with several drug classes	Noted with several members of the drug class

Akt indicates Akt/protein kinase B; AMPK, adenosine monophosphate‐activated protein kinase; mTOR, mammalian target of rapamycin; SGLT2, sodium‐glucose cotransporter 2; and SIRT1, sirtuin‐1.