Sodium-Glucose Cotransporter-2 Inhibitors and Cardiovascular Protection Among Patients With Type 2 Diabetes Mellitus: A Systematic Review

Abstract

Background: Accumulating evidence has demonstrated the positive effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors in managing patients with type 2 diabetes mellitus (T2DM). SGLT2 inhibitors protect patients with T2DM from cardiovascular complications and are generally safe.Aim: The aim of this study is to assess the cardiovascular effects of SGLT2 inhibitors in patients with T2DM.Methods: A systematic review was conducted using published English literature in PubMed and Google Scholar databases.Results: Most of the studies showed significant positive cardiovascular effects of SGLT2 inhibitors in patients with and without established cardiovascular disease (CVD). Empagliflozin reduced the risk of cardiovascular death, hospitalization for heart failure (HHF), cardiovascular death or heart failure, and major adverse cardiovascular events (MACE) such as nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death regardless of the number of cardiovascular risk factors. The effects of empagliflozin on cardiovascular events and mortality in patients with coronary artery bypass graft (CABG) were assessed. Further, the efficacy of empagliflozin in three different phenotypic groups, namely, younger patients with shorter duration of T2DM and highest glomerular filtration rate, women without coronary artery disease, and older adults with advanced coronary artery disease plus several comorbidities, was also assessed. The effects of canagliflozin were evaluated in patients with and without a history of CVD and with different body weights, and in those with and without prior heart failure. Treatment with canagliflozin based on multivariable-predicted cardiovascular risk factors prevented heart failure events more than treatment based on glycated hemoglobin and albuminuria alone. The efficacy of dapagliflozin was evaluated in patients with or at risk of atherosclerotic cardiovascular disease (ASCVD), heart failure status, and left ventricular ejection fraction (LVEF), as well as the elderly population. A reduction in HHF or cardiovascular death and insignificant reduction in MACE were noted. Furthermore, significant reduction in the risk of cardiovascular death and all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF) was also observed. Sotagliflozin was studied for its cardiovascular outcomes in patients with chronic kidney disease with or without albuminuria and resulted in a reduction in cardiovascular-related deaths and HHF.Conclusion: SGLT2 inhibitors have beneficial cardiovascular effects in patients with T2DM and should be incorporated into their management.