title: Inhibition of renal glucose reabsorption as a novel treatment for diabetes patients.
abstract: The importance of the kidney in glucose homeostasis has been recognized for many years. Recent observations indicating a greater role of renal glucose metabolism in various physiologic and pathologic conditions have rekindled the interest in renal glucose handling as a potential target for the treatment of diabetes. The enormous capacity of the proximal tubular cells to reabsorb the filtered glucose load entirely, utilizing the sodium-glucose co-transporter system (primarily SGLT-2), became the focus of attention. Original studies conducted in experimental animals with the nonspecific SGLT inhibitor phlorizin showed that hyperglycemia after pancreatectomy decreased as a result of forced glycosuria. Subsequently, several compounds with more selective SGLT-2 inhibition properties ("second-generation") were developed. Some agents made it into pre-clinical and clinical trials and a few have already been approved for commercial use in the treatment of type 2 diabetes. In general, a 6-month period of therapy with SGLT-2 inhibitors is followed by a mean urinary glucose excretion rate of ~80 g/day accompanied by a decline in fasting and postprandial glucose with average decreases in HgA1C ~1.0%. Concomitant body weight loss and a mild but consistent drop in blood pressure also have been reported. In contrast, transient polyuria, thirst with dehydration and occasional hypotension have been described early in the treatment. In addition, a significant increase in the occurrence of uro-genital infections, particularly in women has been documented with the use of SGLT-2 inhibitors.
  
  
  CONCLUSIONS
  Although long-term cardiovascular, renal and bone/mineral effects are unknown SGLT-2 inhibitors, if used with caution and in the proper patient provide a unique insulin-independent therapeutic option in the management of obese type 2 diabetes patients.
authors.affiliation: Health Science Center San Antonio, University of Texas, Texas.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Cersosimo
authors.affiliation: Health Science Center San Antonio, University of Texas, Texas.
authors.forename: Carolina
authors.initials: C
authors.lastname: Solis-Herrera
authors.affiliation: Health Science Center San Antonio, University of Texas, Texas.
authors.forename: Curtis
authors.initials: C
authors.lastname: Triplitt
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D065608:Renal Reabsorption / Q000187:drug effects*; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors*
chemical_list: D051247:Sodium-Glucose Transport Proteins; D005947:Glucose