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.
CONCLUSION: 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.