title: Empagliflozin, a novel potent and selective SGLT-2 inhibitor, improves glycaemic control alone and in combination with insulin in streptozotocin-induced diabetic rats, a model of type 1 diabetes mellitus.
abstract: OBJECTIVE
  Sodium glucose cotransporter-2 (SGLT-2) is key to reabsorption of glucose in the kidney. SGLT-2 inhibitors are in clinical development for treatment of type 2 diabetes mellitus (T2DM). The mechanism may be of value also in the treatment of type 1 diabetes mellitus (T1DM). This study investigated effects of the SGLT-2 inhibitor, empagliflozin, alone and in combination with insulin, on glucose homeostasis in an animal model of T1DM.
  
  
  METHODS
  Sprague-Dawley rats were administered a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg). Acutely, STZ rats received two doses of insulin glargine with or without empagliflozin, and blood glucose was measured. In a subchronic study, STZ rats received empagliflozin alone, one or two insulin-releasing implants or a combination of one implant and empagliflozin over 28 days; blood glucose and HbA(1c) were measured.
  
  
  RESULTS
  In the acute setting, empagliflozin in combination with 1.5 IU insulin induced a similar glucose-lowering effect as 6 IU insulin. Both interventions were more efficacious than monotherapy with 1.5 IU insulin. In the subchronic study, 12-h blood glucose profile on day 28 in the combination group was lower than with one implant, and similar to two implants. Plasma HbA(1c) was improved in the combination group and in animals with two implants.
  
  
  CONCLUSIONS
  Empagliflozin reduced blood glucose levels in a T1DM animal model. Empagliflozin combined with low-dose insulin showed comparable glucose-lowering efficacy to treatment with high-dose insulin. Our data suggest that empagliflozin is an efficacious adjunctive-to-insulin therapy with the clinical potential for the treatment of T1DM.
authors.affiliation: Department of CardioMetabolic Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, Biberach an der Riss, Germany. gerd.luippold@boehringer-ingelheim.com
authors.forename: G
authors.initials: G
authors.lastname: Luippold
authors.forename: T
authors.initials: T
authors.lastname: Klein
authors.forename: M
authors.initials: M
authors.lastname: Mark
authors.forename: R
authors.initials: R
authors.lastname: Grempler
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005960:Glucosides / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013311:Streptozocin / Q000494:pharmacology*
chemical_list: D001559:Benzhydryl Compounds; D001786:Blood Glucose; D005960:Glucosides; D006442:Glycated Hemoglobin; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013311:Streptozocin; C490300:Slc5a2 protein, rat; C570240:empagliflozin