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Metabolic and neuroprotective effects of dapagliflozin and liraglutide in diabetic mice

Millar, P, Pathak, N, Parthsarathy, Vadivel, Bjourson, AJ, O'Kane, M, Pathak, V, Moffett, Charlotte, Flatt, Peter and Gault, Victor A (2017) Metabolic and neuroprotective effects of dapagliflozin and liraglutide in diabetic mice. Journal of Endocrinology, 234 (3). pp. 255-267. [Journal article]

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DOI: 10.1530/JOE-17-0263


This study assessed the metabolic and neuroprotective actions of the sodium glucose co-transporter-2 inhibitor dapagliflozin in combination with the GLP-1 agonist liraglutide in dietary-induced diabetic mice. Mice administered low-dose streptozotocin (STZ) on a high fat diet received dapagliflozin, liraglutide, dapagliflozin-plus-liraglutide (DAPA-Lira) or vehicle once-daily over 28 days. Energy intake, body weight, glucose and insulin concentrations were measured at regular intervals. Glucose tolerance, insulin sensitivity, hormone and biochemical analysis, dual-energy x-ray absorptiometry densitometry, novel object recognition, islet and brain histology were examined. Once-daily administration of DAPA-Lira resulted in significant decreases in body weight, fat mass, glucose and insulin concentrations, despite no change in energy intake. Similar beneficial metabolic improvements were observed regarding glucose tolerance, insulin sensitivity, HOMA-IR, HOMA-β, HbA1c, and triglycerides. Plasma glucagon, GLP-1 and IL-6 levels were increased and corticosterone concentrations decreased. DAPA-Lira treatment decreased alpha cell area and increased insulin content compared to dapagliflozin monotherapy. Recognition memory was significantly improved in all treatment groups. Brain histology demonstrated increased staining for doublecortin (number of immature neurons) in dentate gyrus and synaptophysin (synaptic density) in stratum oriens and stratum pyramidale. These data demonstrate that combination therapy of dapagliflozin and liraglutide exerts beneficial metabolic and neuroprotective effects in diet-induced diabetic mice. Our results highlight important personalised approach in utilising liraglutide in combination with dapagliflozin, instead of either agent alone, for further clinical evaluation in treatment of diabetes and associated neurodegenerative disorders.

Item Type:Journal article
Keywords:dapagliflozin; diabetes; GLP-1; glucagon; liraglutide
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Stratified Medicine
Biomedical Sciences Research Institute > Diabetes
ID Code:38324
Deposited By: Dr Nigel Irwin
Deposited On:04 Jul 2017 08:47
Last Modified:24 Jun 2018 22:23

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