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Treatment of clozapine-associated obesity and diabetes with exenatide (CODEX) in adults with schizophrenia: study protocol for a pilot randomised controlled trial

  • Karla Mayfield (a1), Dan Siskind (a2) (a3), Karl Winckel (a1) (a4), Samantha Hollingworth (a1), Steve Kisely (a3) and Anthony W. Russell (a3) (a5)...
Abstract
Background

Clozapine causes significant metabolic disturbances including obesity and type 2 diabetes. Recent evidence that reduced glucagon-like-peptide-1 (GLP-1) may contribute to aetiology of clozapine-associated metabolic dysregulation suggests a potential therapeutic role for GLP-1 agonists.

Method

This open-label, pilot randomised controlled trial evaluates the effect of exenatide in clozapine-treated obese adults who have schizophrenia, with or without poorly controlled diabetes. Sixty out-patients will be randomised to once weekly extended release exenatide or treatment as usual for 24 weeks.

Aims

To evaluate the feasibility of larger studies regarding methodology, acceptability, tolerability and estimate efficacy for glycaemic control or weight loss. Secondary outcomes are psychosis severity and metabolic parameters.

Conclusions

This is the first trial investigating GLP-1 agonists for glycaemic control and weight loss in clozapine-treated patients with either diabetes or obesity. Clozapine-associated obesity and diabetes with exenatide (CODEX) will provide proof-of-concept empirical evidence addressing whether this novel treatment is practical and worthy of further investigation.

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Copyright
This is an Open Access article, distributed under the terms of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Corresponding author
Dan Siskind, Metro South Addiction and Mental Health Service 519 Kessels Rd, MacGregor, QLD 4109, Australia. Email: d.siskind@uq.edu.au
Footnotes
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Declaration of interest

A.W.R. has received speaker honoraria and travel grants from AstraZeneca, BoehringerIngelheim, Eli Lilly, MSD, Novo Nordisk and Sanofi and has participated on advisory panels for MSD and Novo Nordisk.

Footnotes
References
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Treatment of clozapine-associated obesity and diabetes with exenatide (CODEX) in adults with schizophrenia: study protocol for a pilot randomised controlled trial

  • Karla Mayfield (a1), Dan Siskind (a2) (a3), Karl Winckel (a1) (a4), Samantha Hollingworth (a1), Steve Kisely (a3) and Anthony W. Russell (a3) (a5)...
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