title: Effects of SGLT2 inhibitors on cardiovascular outcomes.
abstract: Glucose in the glomerular ultrafiltrate is actively reabsorbed by sodium glucose transporters (SGLT) in the proximal tubule. The SGLT2 protein is a high capacity molecule responsible for the majority of glucose reuptake with pharmacological inhibition, resulting in the loss of about 80g of glucose in the urine each day. About a dozen inhibitors of SGLT2 have entered clinical development, and the first has recently been submitted for registration with the United States Food and Drug Administration. The rationale for the clinical evaluation of these agents is their beneficial effects on glycaemia, blood pressure and body weight. No adequately powered trial has yet determined the effects of an SGLT2 inhibitor on either macrovascular or microvascular outcomes, although a number of large-scale trials are now ongoing. Evidence that will define the overall balance of benefits and risks of this new drug class is anticipated within the next 5 years.
authors.affiliation: The George Institute for Global Health, University of Sydney, Australia. cfoote@george.org.au
authors.forename: Celine
authors.initials: C
authors.lastname: Foote
authors.forename: Vlado
authors.initials: V
authors.lastname: Perkovic
authors.forename: Bruce
authors.initials: B
authors.lastname: Neal
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D015195:Drug Design; D019317:Evidence-Based Medicine; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C089180:SLC5A2 protein, human; C517652:hemoglobin A1c protein, human