SGLT-2 Inhibitors and Cardiovascular Protection: Lessons and Gaps in Understanding the Current Outcome Trials and Possible Benefits of Combining SGLT-2 Inhibitors With GLP-1 Agonists

Landmark trials on diabetes control have shown variable results in terms of cardiovascular benefits, with the majority showing a favorable effect of glycemic control on microvascular and, more recently, macrovascular complications. However, some trials pointed out a CV hazard with tight diabetes mellitus (DM) control. Most of those trials were assessing the impact of glycemic control, more than evaluating the effect of a certain medication. In the last decade, food and drugs administration (FDA) has mandated that all new hypoglycemic agents run a CV outcome trial (CVOT) for safety in order to grant and sustain approval. The most stunning results came from relatively new agents in the field of diabetes management, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and the glucagon-like peptide-1 agonists (GLP-1 agonists), details of these CVOTs will be addressed later in this document. SGLT2i effect on the cardiovascular system remains an area of extensive research. We aimed in this review to summarize what is the current evidence of cardiovascular protection upon using SGLT2i. Moreover, we wanted to raise a point that may be strongly adopted in the future, combining SGLT2i plus GLP-1 agonists, having a cardiovascular privilege in both molecules.