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J Psychopharmacol. 2018 May;32(5):578-590. doi: 10.1177/0269881118756061. Epub 2018 Mar 1.

Liraglutide prevents metabolic side-effects and improves recognition and working memory during antipsychotic treatment in rats.

Babic I1,2,3,4, Gorak A2,4, Engel M1,2, Sellers D2,4, Else P2,4, Osborne AL1,3,4, Pai N2,3,4, Huang XF1,2,4, Nealon J2,4, Weston-Green K1,2,4.

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1 Centre for Medical and Molecular Bioscience, Faculty of Science, Medicine and Health, University of Wollongong, NSW, Australia.
2 Illawarra Health and Medical Research Institute, Wollongong, NSW, Australia.
3 Illawarra and Shoalhaven Local Health District, Wollongong, NSW, Australia.
4 School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, NSW, Australia.



Antipsychotic drugs (APDs), olanzapine and clozapine, do not effectively address the cognitive symptoms of schizophrenia and can cause serious metabolic side-effects. Liraglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist with anti-obesity and neuroprotective properties. The aim of this study was to examine whether liraglutide prevents weight gain/hyperglycaemia side-effects and cognitive deficits when co-administered from the commencement of olanzapine and clozapine treatment.


Rats were administered olanzapine (2 mg/kg, three times daily (t.i.d.)), clozapine (12 mg/kg, t.i.d.), liraglutide (0.2 mg/kg, twice daily (b.i.d.)), olanzapine + liraglutide co-treatment, clozapine + liraglutide co-treatment or vehicle (Control) ( n = 12/group, 6 weeks). Recognition and working memory were examined using Novel Object Recognition (NOR) and T-Maze tests. Body weight, food intake, adiposity, locomotor activity and glucose tolerance were examined.


Liraglutide co-treatment prevented olanzapine- and clozapine-induced reductions in the NOR test discrimination ratio ( p < 0.001). Olanzapine, but not clozapine, reduced correct entries in the T-Maze test ( p < 0.05 versus Control) while liraglutide prevented this deficit. Liraglutide reduced olanzapine-induced weight gain and adiposity. Olanzapine significantly decreased voluntary locomotor activity and liraglutide co-treatment partially reversed this effect. Liraglutide improved clozapine-induced glucose intolerance.


Liraglutide co-treatment improved aspects of cognition, prevented obesity side-effects of olanzapine, and the hyperglycaemia caused by clozapine, when administered from the start of APD treatment. The results demonstrate a potential treatment for individuals at a high risk of experiencing adverse effects of APDs.


Cognition; antipsychotic; glucagon-like peptide-1; liraglutide; obesity


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