The Role of Kidney in Glucose Homeostasis — SGLT2 Inhibitors, a New Approach in Diabetes Treatment

Vasileios Andrianesis; John Doupis


Expert Rev Clin Pharmacol. 2013;6(5):519-539. 

In This Article

Familial Renal Glucosuria

Mutations in the transporters, also known to be involved in the tubular glucose reabsorption, are related to congenital diseases. Studies on patients with these diseases may be helpful to better understand the specific role of the transporters and possibly develop new therapeutic agents for diabetes. Fanconi–Brickel syndrome is associated with GLUT2 gene mutation and GLUT2 deficiency.[44] It causes a type of glycogen storage disease with hepatomegaly, tubular nephropathy, glucose and galactose intolerance, fasting hypoglycemia and postprandial hyperglycemia.[45] Glucose–galactose malabsorption is associated with mutation in SGLT1 and familial renal glucosuria (FRG) with mutation in SGLT2. Renal Fanconi syndrome is associated with excessive urinary excretion of glucose, amino acids, phosphate and other solutes, where as in FRG, the excretion is limited to glucose without generalized proximal tubular dysfunction or hyperglycemia. Mild cases of glucosuria (<10 g/day) are related to heterozygosity for SGLT2 mutations and severe cases (>10 g/day) to homozygosity. The most common manifestations of FRG are polyuria, enuresis, growth and maturation delay[46] and only in rare and severe cases can be observed dehydration and ketosis during starvation, pregnancy[47] or urinary tract infections.[48] In general, FRG is not followed by severe symptoms and it can be considered rather a benign differentiation of glucose retention than disease.[49] These observations and the lately conducted clinical studies on SGLT2 inhibitors have established the belief that SGLT2 inhibition may be a possible therapeutic target for type 2 diabetes.