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.
AD - The George Institute for Global Health, University of Sydney, Level 10, King George V Building, Royal Prince Alfred Hospital, Missenden Road, Camperdown, Sydney NSW 2050, Australia. Email: cfoote@george.org.au. AN - 22381403 BT - Diabetes and Vascular Disease Research ET - 2012/03/03 LA - eng M1 - 2 N1 - Foote, CelinePerkovic, VladoNeal, BruceEnglandDiabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular DiseaseDiab Vasc Dis Res. 2012 Apr;9(2):117-23. Epub 2012 Mar 1. N2 -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.
PY - 2012 SN - 1752-8984 (Electronic)1479-1641 (Linking) SP - 117 EP - 23 T2 - Diabetes and Vascular Disease Research TI - Effects of SGLT2 inhibitors on cardiovascular outcomes VL - 9 ER -