Sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus without established cardiovascular disease: do they have a role in primary prevention?

Most guidelines and cardiovascular outcome trials (CVOTs) focus on secondary prevention of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). Patients with T2DM without established CVD (eCVD) also form a critical cohort, for whom primary prevention with timely pharmacological and non-pharmacological interventions can effectively prevent or delay the onset of CVD. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated a promising role for primary prevention of CVD in CVOTs and real-world studies. The 2019 American College of Cardiology/American Heart Association guidelines on primary prevention of CVD recommend SGLT2i as one of the add-on treatment options to metformin for adults with T2DM and glycated hemoglobin >7% who have cardiovascular (CV) risk factors. The outcomes with maximal response to SGLT2i use in primary prevention are hospitalization for heart failure and chronic kidney disease. The cardiorenal benefits with SGLT2i are attributed to pleiotropic effects on CV risk factors, and interference with glucose and sodium handling in kidneys, independent of their glycemic benefits. Results therefore support a role for SGLT2i not only in patients with T2DM and eCVD but also in patients with T2DM without eCVD. This review examines the evidence for potential role of SGLT2i for primary prevention of CVD in T2DM.