The effects of sodium-glucose cotransporter 2 inhibitors on left ventricular function: current evidence and future directions

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a unique class of oral anti-hyperglycaemic medications that act to reduce glucose reabsorption in the renal proximal tubules, thereby enhancing urinary glucose excretion. Large randomized placebo-controlled trials in people with diabetes at high cardiovascular risk have demonstrated that SGLT2 inhibitors reduce heart failure hospitalization within months of commencing therapy. These findings are of considerable interest, as diabetes is associated with an increased risk of both heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. In addition, left ventricular (LV) hypertrophy and impaired diastolic function is thought to be more prevalent in people with diabetes. Although many hypotheses have been proposed, the underlying mechanisms through which SGLT2 inhibitors reduce the risk of heart failure in people with diabetes are not fully understood. Given the rapid reduction in heart failure hospitalization, it is conceivable that the benefits of SGLT2 inhibitors are due to favourable haemodynamic and metabolic effects on LV function. Several clinical studies have been conducted to investigate the effect of SGLT2 inhibitors on LV structure and function and have found that LV mass index and diastolic function improve following SGLT2 inhibitor therapy in people with type 2 diabetes. If these findings are confirmed in future studies utilizing novel cardiac imaging modalities and large randomized controlled trials, then this will bring new hope for the prevention and management of heart failure with preserved ejection fraction, for which no current treatments have been shown to reduce mortality. At the present time, SGLT2 inhibitors are indicated for the treatment of type 2 diabetes; however, the results of ongoing trials in participants with heart failure but without diabetes are eagerly awaited. The purpose of this review is to summarize current knowledge regarding the effects of SGLT2 inhibitors on LV function, particularly the findings from clinical studies, proposed biological mechanisms, and future directions.

Keywords: Diabetes mellitus; Echocardiography; Heart failure; Prevention; SGLT2 inhibitor; Treatment.