Sodium-Glucose Co-Transporter 2 Inhibitors and the Potential for Cardiovascular Risk Reduction in Patients With Type 2 Diabetes Mellitus

Background: Clinical development programs of investigational antidiabetic agents now include evaluation of cardiovascular (CV) risk as a major research focus. Recently, several compounds in a new class of antihyperglycemic therapy have reached the final stages of development. Treatment with inhibitors of sodium-glucose co-transporters 2 (SGLT2) leads to urinary excretion of glucose in patients with type 2 diabetes mellitus (T2DM), and is associated with clinically significant reductions in blood glucose levels. The glucosuria-based mechanism of this class has the potential to induce weight loss through reduced caloric availability, and, in addition, may affect blood pressure (BP) via osmotic diuresis or other as yet incompletely characterized mechanisms. Methods: Searches of the PubMed database were conducted for published studies evaluating the use of SGLT2 inhibitors that reported data on CV risk factors (eg, weight, BP, lipid levels) or CV events. Searches for presentations at recent major diabetes congresses were performed using the Online Abstract Submission and Invitation System. Results: Treatment with SGLT2 inhibitors has consistently been associated with reduction in body weight and BP. Qualitative graphical assessment of 21 studies shows unadjusted reductions in systolic BP and body weight typically ranging between 3 to 5 mm Hg and 2 to 3 kg, respectively. A few reports have suggested the potential for improvement in lipid parameters, such as high-density lipoprotein cholesterol levels; however, not all studies have demonstrated significant changes, and some have noted small increases in low-density lipoprotein cholesterol levels. Conclusion: Inhibition of SGLT2 in patients with T2DM may be associated with significant weight loss and BP reduction that are sustainable over the average time span of an investigational clinical study (ie, 3-6 months). When considered in terms of the potential for combination therapy, these features may offer a means of further reducing metabolic and CV risk in patients with T2DM.