title: Sodium-glucose linked transporter-2 inhibitors: potential for renoprotection beyond blood glucose lowering?
abstract: The proximal tubule's sodium-glucose linked transporter-2 (SGLT2) accounts for the vast majority of glucose reabsorption by the kidney. Its selective inhibition, accordingly, leads to substantial glycosuria, lowering blood glucose, and facilitating weight loss in individuals with diabetes. During the past year, two SGLT2 inhibitors, canagliflozin and dapagliflozin, have been approved for the treatment of type 2 diabetes. Beyond their anti-hyperglycemic properties, however, this new class of drugs has several other attributes that provide a theoretical basis for kidney protection. Like agents that block the renin-angiotensin system, SGLT2 inhibitors also reduce single-nephron glomerular filtration rate (SNGFR) in the chronically diseased kidney, though by quite different mechanisms. Additional potentially beneficial effects of SGLT2 inhibition include modest reductions in blood pressure and plasma uric acid. Finally, cell culture studies indicate that glucose uptake from the tubular lumen, as well as from the basolateral compartment, can contribute to proximal tubular production of extracellular matrix proteins. Whether such attributes will translate into reducing the progression of chronic kidney disease will require the undertaking of long-term, dedicated studies.
authors.affiliation: Division of Endocrinology, Department of Medicine, University of Toronto, St Michael's Hospital, Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Gilbert
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D000068896:Canagliflozin; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D003928:Diabetic Nephropathies / Q000188:drug therapy; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism*; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007678:Kidney Glomerulus / Q000187:drug effects / Q000502:physiology; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use; D014527:Uric Acid / Q000097:blood
chemical_list: D001559:Benzhydryl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013876:Thiophenes; D000068896:Canagliflozin; C529054:dapagliflozin; D014527:Uric Acid; D005947:Glucose