title: Combined antidiabetic benefits of exenatide and dapagliflozin in diabetic mice.
abstract: The combined glucose-lowering effect of exenatide and dapagliflozin has not yet been studied. We investigated this combination (single-dose or 4-week dosing) in diabetic ob/ob mice. Vehicle-corrected basal glucose showed greater reduction 1 h following exenatide + dapagliflozin than with exenatide or dapagliflozin alone, and stayed significantly lower for all groups versus vehicle over 3 h. During an oral glucose tolerance test, glucose excursion (30 min post-dose) was significantly lower for exenatide + dapagliflozin versus exenatide or dapagliflozin, or vehicle. Exenatide + dapagliflozin and exenatide, but not dapagliflozin alone, reduced glucose excretion over 24 h versus vehicle. After dosing for 4 weeks, exenatide, dapagliflozin and exenatide + dapagliflozin similarly decreased haemoglobin A1c (HbA1c). Body weight was reduced only with exenatide or exenatide + dapagliflozin. The glomerular filtration rate was similar with exenatide, dapagliflozin and vehicle, and increased with exenatide + dapagliflozin. Optimized combinatorial dosing of these antidiabetic agents may provide additive glucose lowering in type 2 diabetes mellitus.
authors.affiliation: Amylin Pharmaceuticals, LLC, San Diego, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Tatarkiewicz
authors.forename: C
authors.initials: C
authors.lastname: Polizzi
authors.forename: C
authors.initials: C
authors.lastname: Villescaz
authors.forename: L J
authors.initials: LJ
authors.lastname: D'Souza
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Janssen
authors.forename: D G
authors.initials: DG
authors.lastname: Parkes
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D000077270:Exenatide; D005960:Glucosides / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D010455:Peptides / Q000494:pharmacology*; D014688:Venoms / Q000494:pharmacology*
chemical_list: D001559:Benzhydryl Compounds; D015415:Biomarkers; D001786:Blood Glucose; D000077270:Exenatide; D005960:Glucosides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; C529054:dapagliflozin
keywords: combination; dapagliflozin; diabetes; exenatide; glucagon-like peptide-1; mouse