Clinical Evidence and Proposed Mechanisms for Cardiovascular and Kidney Benefits from Sodium–Glucose Co-transporter-2 Inhibitors

The number of people living with type 2 diabetes (T2D) and its complications worldwide is increasing at an alarming rate. Fortunately, our understanding of the benefits of glucose-lowering agents from the sodium–glucose co-transporter-2 (SGLT2) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist classes on cardiovascular and kidney outcomes is advancing; this means we now have new options to mitigate the risks of these complications in patients with T2D. The SGLT2 inhibitors have consistently demonstrated benefits on atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) and heart failure (HF) events in dedicated outcome trials. Large guidelines groups now recommend SGLT2 inhibitors as a standard of care in patients with T2D and comorbid ASCVD, CKD and/ or HF. Evolving evidence additionally indicates kidney and HF benefits of SGLT2 inhibitors in populations without diabetes. These agents likely provide heart and kidney benefits through multiple mechanisms, as their impact on heart and kidney outcomes cannot be fully explained by their direct metabolic effects. On-going work to elucidate the beneficial mechanisms at play with SGLT2 inhibitors will help further optimize these life-saving therapies in patients with and without T2D.