Journal Article

Potential Mechanisms of Sodium-Glucose Co-Transporter 2 Inhibitor-Related Cardiovascular Benefits

Verma, Subodh

2019

Overview

The findings of recent clinical trials have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors produce effects beyond glucose lowering and have demonstrated beneficial cardiovascular effects that have been observed across a broad range of patients with type 2 diabetes mellitus. In particular, the cardiovascular benefit results largely from substantial and early effects of SGLT2 inhibition on cardiovascular death and hospitalization for heart failure. Recent cardiovascular outcomes trials (CVOTs) have also shown that relative risk reductions in cardiovascular outcomes were observed with SGLT2 inhibition both in patients with current and prior heart failure. Since the observed reductions of cardiovascular outcomes with SGLT2 inhibitor therapy were observed much earlier than would be expected by an anti-atherosclerotic effect, these results have led to speculation about the potential underlying pathways. Suggested mechanisms include natriuresis and osmotic diuresis; reductions in inflammation, oxidative stress, and arterial stiffness; reductions in blood pressure and body weight; and possible renoprotective effects. These effects could produce cardiovascular benefits through a range of cardiac effects, including reduction in left ventricular load, attenuation of cardiac fibrosis and inflammation, and improved myocardial energy production. Other possible mechanisms include inhibition of sodium-hydrogen exchange, increases in erythropoietin levels, and reduction in myocardial ischemia or reperfusion injury. It is likely that a range of mechanisms underlie the observed cardiovascular benefits of SGLT2 inhibitors; further elucidation of these mechanisms will be answered by ongoing research.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Arteriosclerosis / Atherosclerosis / Attenuation / Blood pressure / Blood Pressure - drug effects / Body weight / Body Weight - drug effects / Cardiovascular disease / Cardiovascular Diseases / Cardiovascular System - drug effects / Clinical trials / Congestive heart failure / Diabetes mellitus / Diabetes mellitus (non-insulin dependent) / Diuresis / Diuresis - drug effects / Diuretics / Erythropoietin / Fibrosis / Glucose / Glucose transporter / Health risk assessment / Heart - drug effects / Humans / Hydrogen exchange / Inflammation / Inhibitors / Injury prevention / Ischemia / Kidney - drug effects / Mortality / Myocardial Ischemia / Myocardial Reperfusion Injury / Myocardium - metabolism / Natriuresis - drug effects / Oxidative stress / Oxidative Stress - drug effects / Reperfusion / Sodium / Sodium-Glucose Transporter 2 Inhibitors - pharmacology / Sodium-Hydrogen Exchangers / Stiffness / Vascular Stiffness - drug effects / Ventricle