Cerebrovascular Complications of Diabetes: SGLT-2 Inhibitors as a Promising Future Therapeutics

Abstract

Sodium-Glucose co-transporter inhibitors are a novel class of drugs widely used in the treatment of type 2 diabetes mellitus medical management. This class of drugs has a simple mechanism of action by which they decrease blood glucose levels. They prevent the uptake or re-absorption of glucose in the blood by inhibiting the SGLT2 co-transport channels located in the renal proximal convoluted tubule. Since SGLT2 is the low affinity, high capacity glucose transporter, it allows the co-transport of sodium and glucose through it. SGLT2s are accountable for around 90% of the renal glucose reuptake. Cerebrovascular complications or accidents (CVAs) are the world's leading cause of mortality, resulting in around 6 million deaths annually. Diabetics are prone to develop mitochondrial dysfunction and neurodegeneration due to hyperglycemia and oxidative stress end products. Due to hyperglycemic condition in diabetes, it is always an elevated risk of cerebrovascular dysfunction due to hyperglycemia as it includes endothelial dysfunction, atherosclerosis, hypercoagulability, oxidative stress, renal reperfusion injury which may lead to neuronal degeneration and cognitive impairment. A diabetic individual is more prone to develop risk factors for transient ischemic attacks than a non-diabetic patient. These inhibitors reduce hyperglycemia by blocking renal glucose reabsorption, therefore promoting an increase in renal glucose excretion. This review discusses the potential role of SGLT2 inhibitors in treating CVAs associated with T2DM.