title: Glucagon-like peptide-1 agonists combating clozapine-associated obesity and diabetes.
abstract: Clozapine is the most effective antipsychotic, but its use is tempered by adverse metabolic effects such as weight gain, glucose intolerance and type II diabetes. Current interventions do not facilitate compelling or sustained improvement in metabolic status. Recent studies suggest that glucagon-like peptide-1 (GLP-1) may play a key role in clozapine's metabolic effects, possibly suggesting that clozapine-associated obesity and diabetes are mediated independently through reduced GLP-1. As a result, GLP-1 agonists could show promise in reversing antipsychotic-induced metabolic derangements, providing mechanistic justification that they may represent a novel approach to treat, and ultimately prevent, both diabetes and obesity in patients on clozapine. GLP-1 agonists are already used for diabetes, and they provide a unique combination of glycaemic improvement and metabolically relevant weight loss in diabetic and non-diabetic patients, in the context of a currently favourable safety proﬁle. Using GLP-1 agonists for clozapine-associated obesity and diabetes could be a potentially effective intervention that may reduce cardiometabolic morbidity and mortality in this vulnerable patient population.
authors.affiliation: School of Pharmacy, University of Queensland, Pharmacy Australia Centre of Excellence, Brisbane, QLD, Australia.
authors.forename: Karla
authors.initials: K
authors.lastname: Mayfield
authors.affiliation: Metro South Addiction and Mental Health Service, Princess Alexandra Hospital, Brisbane, QLD, Australia School of Medicine, University of Queensland, Brisbane, QLD, Australia d.siskind@uq.edu.au.
authors.forename: Dan
authors.initials: D
authors.lastname: Siskind
authors.affiliation: School of Pharmacy, University of Queensland, Pharmacy Australia Centre of Excellence, Brisbane, QLD, Australia Pharmacy Department, Princess Alexandra Hospital, Brisbane, QLD, Australia.
authors.forename: Karl
authors.initials: K
authors.lastname: Winckel
authors.affiliation: School of Medicine, University of Queensland, Brisbane, QLD, Australia Department of Diabetes and Endocrinology, Princess Alexandra Hospital, Brisbane, QLD, Australia.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Russell
authors.affiliation: Metro South Addiction and Mental Health Service, Princess Alexandra Hospital, Brisbane, QLD, Australia School of Medicine, University of Queensland, Brisbane, QLD, Australia.
authors.forename: Steve
authors.initials: S
authors.lastname: Kisely
authors.affiliation: School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Smith
authors.affiliation: School of Pharmacy, University of Queensland, Pharmacy Australia Centre of Excellence, Brisbane, QLD, Australia.
authors.forename: Samantha
authors.initials: S
authors.lastname: Hollingworth
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D003024:Clozapine / Q000009:adverse effects*; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced* / Q000188:drug therapy*; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D006801:Humans; D009765:Obesity / Q000139:chemically induced* / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D052216:Glucagon-Like Peptide 1; D003024:Clozapine
keywords: Clozapine; GLP-1; antipsychotic; metabolic; schizophrenia