The Role of SGLT2 Inhibitors on Treatment of Heart Failure, Mode of Actions

Sodium glucose co-transporter 2 (SGLT2) inhibitors have been in use for treating type 2 diabetes with recent advances in treating heart failure, especially in the context of patients with or without diabetes. SGLT2i has broader effects than diabetic control for treating heart failure, which operates through several interwoven pathways. Their diuretic effects cause a reduction in blood volume, which, in turn, results in preload decline in the heart. Lower preload can benefit patients with heart failure since it reduces congestion and edema. SGLT2 inhibitors promote the excretion of glucose and Na+ in the urine, lowering plasma volume. Lowered plasma volume decreases the workload on the heart and improves cardiac function, especially in patients with HFrEF. SGLT2is has been shown to shift cardiac metabolism from fatty-acid use to more efficient glucose use. SGLT2 inhibitors have mitigated cardiac remodeling, reducing myocardial fibrosis, hypertrophy, and inflammation. SGLT2 inhibitors have been found to lower blood pressure, which can be beneficial in the management of heart failure, especially in patients with hypertension. Clinical trials where SGLT2is showed significantly lowered risks of adverse cardiovascular events, including HF hospitalizations, cardiovascular mortality, and all-cause mortality in patients with heart failure with and without diabetes.