sergliflozin-etabonate and dapagliflozin

Current options for glycemic control are less than optimal in terms of efficacy and to reduce complications in the diabetic population. Selective inhibition of SGLT2 in the proximal tubule increases urinary glucose excretion thereby reducing plasma glucose levels, which may present a novel therapeutic approach.. SGLT2 inhibitors enhance glucose excretion and improve glycemic control in patients with type 2 diabetes in the absence of clinically relevant hypoglycemia or sustained changes in volume status or glomerular filtration rate. This is associated with lowering of body weight and may reduce systolic blood pressure. The increased glucosuria appears to increase the risk of genital infections but may not increase the risk of urinary tract infections.. The ability of SGLT2 inhibitors to reduce plasma glucose without inducing increased insulin secretion, clinically relevant hypoglycemia, or weight gain constitutes a major advance. The ability to increase glucose excretion provides a powerful means to treat caloric excess conditions. Important questions remain to be resolved and more clinical research is needed on the long-term effects of SGLT2 inhibition. Potential extrarenal effects need to be explored in order to determine the safety of these compounds. It also remains to be determined whether these drugs lower the toxicity of glucose directly on renal cells, independent of hyperglycemia, which may slow or prevent the progressive nature of diabetic nephropathy.

Topics: Absorption; Benzhydryl Compounds; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Glucose; Glucosides; Humans; Kidney; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors

The kidney plays a central role in the regulation of plasma glucose levels, although until recently this has not been widely appreciated or considered a target for therapeutic intervention. The sodium glucose co-transporter type 2 (SGLT2) located in the plasma membrane of cells lining the proximal tubule mediates the majority of renal glucose reabsorption from the tubular fluid, which normally prevents the loss of glucose in the urine. Competitive inhibitors of SGLT2 that provoke the renal excretion of glucose have been discovered, thereby providing a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes.. To explore the physiology of SGLT2 action and discuss several SGLT2 inhibitors that have entered early clinical development.. All publicly available data were identified by searching the internet for 'SGLT2' and 'SGLT2 inhibitor' through 1 November 2007. Published articles, press releases and abstracts presented at national and international meetings were considered.. Sodium glucose co-transporter type 2 inhibition is a novel treatment option for diabetes, which has been studied in preclinical models and a few potent and selective SGLT2 inhibitors have been reported and are currently in clinical development. These agents appear to be safe and generally well tolerated, and will potentially be a beneficial addition to the growing battery of oral antihyperglycaemic agents.

Topics: Adolescent; Adult; Aged; Benzhydryl Compounds; Blood Glucose; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Female; Glucosides; Humans; Hypoglycemic Agents; Male; Middle Aged; Sodium-Glucose Transporter 2 Inhibitors