title: Long-term treatment with empagliflozin, a novel, potent and selective SGLT-2 inhibitor, improves glycaemic control and features of metabolic syndrome in diabetic rats.
abstract: Empagliflozin is a potent, selective sodium glucose co-transporter-2 inhibitor that is in development for the treatment of type 2 diabetes. This series of studies was conducted to assess the in vivo pharmacological effects of single or multiple doses of empagliflozin in Zucker diabetic fatty rats. Single doses of empagliflozin resulted in dose-dependent increases in urinary glucose excretion and reductions in blood glucose levels. After multiple doses (5 weeks), fasting blood glucose levels were reduced by 26 and 39% with 1 and 3 mg/kg empagliflozin, respectively, relative to vehicle. After 5 weeks, HbA1c levels were reduced (from a baseline of 7.9%) by 0.3 and 1.1% with 1 and 3 mg/kg empagliflozin, respectively, versus an increase of 1.1% with vehicle. Hyperinsulinaemic-euglycaemic clamp indicated improved insulin sensitivity with empagliflozin after multiple doses versus vehicle. These findings support the development of empagliflozin for the treatment of type 2 diabetes.
authors: Department of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co.KG, Biberach, Germany. leo.thomas@boehringer-ingelheim.com
authors: L
authors: L
authors: Thomas
authors: R
authors: R
authors: Grempler
authors: M
authors: M
authors: Eckhardt
authors: F
authors: F
authors: Himmelsbach
authors: A
authors: A
authors: Sauer
authors: T
authors: T
authors: Klein
authors: P
authors: P
authors: Eickelmann
authors: M
authors: M
authors: Mark
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects*; D015309:Glucose Clamp Technique; D005960:Glucosides / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000187:drug effects*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000188:drug therapy*; D051381:Rats; D011924:Rats, Zucker; D000077203:Sodium-Glucose Transporter 2 Inhibitors
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C570240:empagliflozin