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.

Keywords: Clozapine; GLP-1; antipsychotic; metabolic; schizophrenia.