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Combined antidiabetic benefits of exenatide and dapagliflozin in diabetic mice
Author(s) -
Tatarkiewicz K.,
Polizzi C.,
Villescaz C.,
D'Souza L. J.,
Wang Y.,
Janssen S.,
Parkes D. G.
Publication year - 2014
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12237
Subject(s) - exenatide , dapagliflozin , medicine , endocrinology , diabetes mellitus , type 2 diabetes , pharmacology
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.