Cardiovascular Benefit of Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitors in Type 2 Diabetes: A Systematic Review

Cardiovascular disease (CVD) is the leading cause of mortality worldwide yet, despite advances in treatment, CVD remains an underestimated and undermanaged condition, with an even greater risk in Type 2 Diabetes Mellitus (T2DM). Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) are a promising novel drug class reported to improve Cardiovascular (CV) and renal outcomes in T2DM. Recent large-scale trials have assessed their CV safety with unexpected findings of multiple systemic benefits that could potentially reverse CVD. In this systematic review, we examined ten Randomized Controlled Trials (RCTs) that looked at cardiovascular outcomes in Type 2 diabetics and SGLT-2i. The RCTs were appropriately screened, looking for clear primary or secondary outcomes on CV events, and compared with placebo or other antidiabetic drugs. The RCTs had an average sample population studied of 5,549 participants with a mean follow-up time of 2.66 years. Three of the studies focused on CV parameters and risk factors. The remaining had defined CV composite events, and all consistently observed at least one CV benefit when using SGLT-2i. Our review of SGLT-2i in Type 2 diabetics showed the greatest benefit in reducing Heart Failure (HF) exacerbation and modest lowering of CV complications in high CV risk participants. Overall, there is still uncertainty about the exact mechanisms of SGLT-2i in their CV benefit, and whether they would favor pre-diabetic populations and those at earlier stages of CVD.