Cardiovascular Protection by Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor: How to Optimize the Agent for Patients?

Abstract

Sodium-glucose co-transporter 2 (SGLT2) inhibitor such as empagliflozin and canagliflozin have been shown to decrease atherosclerotic cardiovascular morbidity and mortality in patients with type 2 diabetes and overt cardiovascular disease (CVD). In the primary analysis, dapagliflozin did not appear to reduce atherosclerotic cardiovascular morbidity or cardiovascular mortality. However, it decreased cardiovascular outcomes in a sub-analysis of the primary trial. The cardiovascular trials to date have been carried out in very high-risk populations to increase the hazard rate for major CVD events and complete the studies in a relatively brief period of time. Compared with the empagliflozin and canagliflozin trials, the dapagliflozin trial had a lower fraction of participants with established CVD and a greater proportion of patients with multiple risk factors for CVD (multiple risk factors in 60 percent compared with 0 and 34 percent in the empagliflozin and canagliflozin trials, respectively). This difference in patient population may explain, in part, the differences in atherosclerotic CVD outcomes. However, the ertugliflozin cardiovascular trial only included patients with established CVD and did not show superior benefit in the composite outcome (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). In patients with type 2 diabetes and heart failure, all SGLT2 inhibitors have shown salutary effects.