title: Sodium-Glucose Cotransporter Inhibitors: Effects on Renal and Intestinal Glucose Transport: From Bench to Bedside.
abstract: Type 2 diabetes is a chronic disease with disabling micro- and macrovascular complications that lead to excessive morbidity and premature mortality. It affects hundreds of millions of people and imposes an undue economic burden on populations across the world. Although insulin resistance and insulin secretory defects play a major role in the pathogenesis of hyperglycemia, several other metabolic defects contribute to the initiation/worsening of the diabetic state. Prominent among these is increased renal glucose reabsorption, which is maladaptive in patients with diabetes. Instead of an increase in renal glucose excretion, which could ameliorate hyperglycemia, there is an increase in renal glucose reabsorption, which helps sustain hyperglycemia in patients with diabetes. The sodium-glucose cotransporter (SGLT) 2 inhibitors are novel antidiabetes agents that inhibit renal glucose reabsorption and promote glucosuria, thereby leading to reductions in plasma glucose concentrations. In this article, we review the long journey from the discovery of the glucosuric agent phlorizin in the bark of the apple tree through the animal and human studies that led to the development of the current generation of SGLT2 inhibitors.
authors.affiliation: Veterans Affairs Medical Center, San Diego, CA School of Medicine, University of California, San Diego, San Diego, CA smudaliar@vapop.ucsd.edu.
authors.forename: Sunder
authors.initials: S
authors.lastname: Mudaliar
authors.affiliation: Janssen Research & Development, LLC, San Diego, CA.
authors.forename: David
authors.initials: D
authors.lastname: Polidori
authors.affiliation: Regeneron Pharmaceuticals, Inc., Tarrytown, NY.
authors.forename: Brian
authors.initials: B
authors.lastname: Zambrowicz
authors.affiliation: Veterans Affairs Medical Center, San Diego, CA School of Medicine, University of California, San Diego, San Diego, CA.
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
mesh_terms: D000818:Animals; D001692:Biological Transport; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006029:Glycosuria / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D010695:Phlorhizin / Q000494:pharmacology*; D065667:Renal Elimination; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D007004:Hypoglycemic Agents; D051247:Sodium-Glucose Transport Proteins; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D010695:Phlorhizin; D005947:Glucose