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Salsalate and/or metformin therapy confer beneficial metabolic effects in olanzapine treated female mice.

Abstract
Antipsychotic medications are used in the management of schizophrenia and a growing number of off-label conditions. While effective at reducing psychoses, these drugs possess noted metabolic side effects including weight gain, liver lipid accumulation and disturbances in glucose and lipid metabolism. To counter the side effects of antipsychotics standard of care has typically included metformin. Unfortunately, metformin does not protect against antipsychotic induced metabolic disturbances in all patients and thus additional treatment approaches are needed. One potential candidate could be salsalate, the prodrug of salicylate, which acts synergistically with metformin to improve indices of glucose and lipid metabolism in obese mice. The purpose of the current investigation was to compare the effects of salsalate, metformin and a combination of both drugs, on weight gain and indices of metabolic health in female mice treated with the antipsychotic, olanzapine. Herein we demonstrate that salsalate was equally as effective as metformin in protecting against olanzapine induced weight gain and liver lipid accumulation with no additional benefit of combining both drugs. Conversely, metformin treatment, either alone or in combination with salsalate, improved indices of glucose metabolism and increased energy expenditure in olanzapine treated mice. Collectively, our findings provide evidence that dual therapy with both metformin and salsalate could be an efficacious approach with which to dampen the metabolic consequences of antipsychotic medications.
AuthorsHesham Shamshoum, Kyle D Medak, Greg L McKie, Stewart Jeromson, Margaret K Hahn, David C Wright
JournalBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 168 Pg. 115671 (Dec 2023) ISSN: 1950-6007 [Electronic] France
PMID37839107 (Publication Type: Journal Article)
CopyrightCopyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
Chemical References
  • Olanzapine
  • Antipsychotic Agents
  • Metformin
  • salicylsalicylic acid
  • Salicylates
  • Lipids
  • Glucose
  • Benzodiazepines
Topics
  • Humans
  • Female
  • Mice
  • Animals
  • Olanzapine
  • Antipsychotic Agents (therapeutic use)
  • Metformin (pharmacology, therapeutic use)
  • Salicylates (pharmacology)
  • Weight Gain
  • Lipids
  • Glucose
  • Benzodiazepines

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