Paradoxical insights into whole body metabolic adaptations following SGLT2 inhibition.
It is well known that glycemic control over time reduces microvascular and macrovascular complications in human subjects with type 2 diabetes. In addition, preclinical models of type 2 diabetes have demonstrated that long-term hyperglycemia exacerbates insulin resistance and reduces β cell function; therefore, therapies that reduce blood glucose levels are of great interest in not only controlling complications, but for restoring known defects in the pathogenesis of type 2 diabetes. Pharmacological inhibition of the sodium-glucose cotransporter 2 (SGLT2) reduces plasma glucose by limiting glucose absorption in the kidney and increasing glucose excretion in the urine. In this issue of the JCI, Merovci and colleagues and Ferrannini and colleagues independently report a paradoxical increase in endogenous glucose production in patients with type 2 diabetes following SGLT2 inhibition, despite an overall decrease in fasting plasma glucose. Together, these studies provide a unique insight into the effects of SGLT2 inhibition on whole body metabolism.
William T
WT
Cefalu
D001559:Benzhydryl Compounds / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D005960:Glucosides / Q000627:therapeutic use*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008297:Male; D009132:Muscles / Q000187:drug effects*; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors
D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D007328:Insulin; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C529054:dapagliflozin; C570240:empagliflozin