To provide a perspective on the effect of Sodium-glucose co-transporter 2 (SGLT2) inhibitors on cardiovascular (CV) risk reduction in type 2 diabetes mellitus (DM) patients.
Sodium-glucose co-transporter 2 inhibitors have been introduced as hypoglycemic agents for the treatment of type 2 diabetes by the unique mechanism of inhibiting the SGLT2 protein-mediated uptake of glucose by the kidney, producing an osmotic diuresis and some degree of natriuresis. The Food and Drug Administration (FDA) has thus far approved three drugs of this class for the treatment of type 2 diabetes – empagliflozin, canagliflozin, and dapagliflozin.
During the clinical trials performed to establish efficacy in diabetes control, these drugs were found to exert a range of beneficial effects beyond glucose lowering. The most interesting of these has been a reduction in systolic blood pressure (SBP) by an average of 3 to 5 mm Hg and diastolic blood pressure (DBP) of 2 to 3 mm Hg. A larger and even more unexpected discovery was that empagliflozin reduced the primary outcome of death from CV causes and nonfatal myocardial infarctions and strokes from 12.1% in the placebo group to 10.5% in an empagliflozin group in a clinical trial enrolling high CV risk patients. Overall, there was a 30 to 40% reduction in heart failure hospitalizations (HFHs) and all-cause deaths, with the event reduction appearing within the first 6 months and persisting to the trial conclusion.
The mechanisms for the aforementioned impressive beneficial events remain unclear, but may involve improvements in such parameters as blood pressure, vascular volume, myocardial glucose availability, reduced arterial vascular stiffness, and improvements in autonomic nervous system function. At this time, all approved SGLT2 inhibitors appear similar in pharmacological actions. Clinical trials are now in progress – or under development – that will further explore the CV actions and outcomes of these drugs.
This review may aid to unify the existing knowledge on SGLT2 inhibitors and CV risk reduction, and set the path for further research endeavors to clarify mechanisms of action associated with additional CV benefits.
How to cite this article
Sander GE, Fernandez C, Kadowitz PJ, Giles TD. Sodium-Glucose Co-transporter 2 Inhibitor: A Perspective on Cardiovascular Risk Reduction in Type 2 Diabetes Mellitus. Hypertens J 2016;2(3):139-144.