The Effects of Sodium-Glucose Co-transporter 2 Inhibitors on Cardiovascular Outcomes in Heart Failure: A Systematic Review and Meta-Analysis

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, initially developed to treat type 2 diabetes mellitus, work by blocking SGLT2 proteins in the proximal convoluted tubules of the nephrons, thereby preventing glucose reabsorption into the bloodstream. Subsequently, its mechanism reveals additional cardiovascular and renal benefits, necessitating further investigation into its effects on heart failure. This condition affects millions and leads to diminished quality of life, frequent hospitalizations, and high mortality rates. This review aims to evaluate several large randomized controlled trials (RCTs) investigating the favourable outcomes of SGLT2 inhibitors on heart failure and its related variables, including hospitalizations secondary to the condition, mortality rate, kidney function, and left ventricular ejection fraction (LVEF). Nine RCTs were reviewed systematically and meta-analyzed to assess the effectiveness of SGLT2 inhibitors. A pooled risk ratio was calculated under a random-effects model, along with heterogeneity analysis, to summarize the overall effect across studies. The studies analyzed two primary clinical outcomes of mortality and rehospitalization due to heart failure. SGLT2 inhibitors were associated with a 20% relative reduction in mortality (risk ratio (RR) = 0.80) and a 24% relative risk reduction of rehospitalization due to heart failure (RR = 0.76). These findings support the cardioprotective effects of SGLT2 inhibitors, as well as significant reductions in hospitalization and mortality. The efficacy of SGLT2 inhibitors was observed across diverse demographic and clinical subgroups, supporting their role as a valuable therapeutic option for managing heart failure.