Treatment of antipsychotic-associated obesity with a GLP-1 receptor agonist: Protocol for an investigator-initiated prospective, randomised, placebo-controlled, double-blinded intervention study – the TAO study

Introduction: Antipsychotic medication is widely associated with dysmetabolism including obesity and type 2 diabetes, cardiovascular-related diseases and early death. Obesity is considered the single most important risk factor for cardiovascular morbidity and mortality. Interventions against antipsychotic-associated obesity are limited and insufficient. Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for the treatment of type 2 diabetes, but their bodyweight lowering effects have also been recognized in non-diabetic patients. The purpose of this trial is to examine if treatment with a GLP-1 receptor agonist (exenatide once-weekly) is safe and facilitates weight loss in non-diabetic schizophrenia patients with antipsychotic-associated obesity.

Methods and analysis: Forty obese patients with schizophrenia or schizoaffective disorder treated with antipsychotic drugs will be randomised to subcutaneous injection of exenatide once-weekly (2 mg) or placebo for 3 months, adjunctive to their antipsychotic treatment. The primary endpoints are safety and weight loss after 3 months. Secondary endpoints include several metabolic measurements, various psychopathological and cognitive measures, and structural and functional brain magnetic resonance imaging.

Ethics and dissemination: The trial has been approved by the Danish Health and Medicines Authority, the National Committee on Health Research Ethics and the Danish Data Protection Agency. Trial participation presupposes both orally and written patient informed consent. An external, independent monitoring committee (Good Clinical Practice Unit at Copenhagen University Hospital) will monitor the study according to the GCP Guidelines. Trial data, including positive, negative and inconclusive results, will be presented at national and international scientific meetings and conferences. Publications will be submitted to peer-reviewed journals.