The glucagon like peptide-1 analogue dulaglutide to prevent antipsychotic induced weight gain – a study protocol proposal

Abstract

Introduction: Schizophrenia spectrum disorders are characterized by delusions, hallucinations and perceptual disturbances and lead to increased personal and economic burden. Besides psychotherapy, antipsychotic medications are the main treatment option, although inducing major side effects. Weight gain is the most common side effect in patients treated with second generation antipsychotics (SGAs), especially in those receiving olanzapine and clozapine. No standard prevention of weight gain for patients receiving these medications has yet been established. The glucagon-like-peptide-1 (GLP-1) analogue dulaglutide (Trulicity®) has been studied in other disease areas as a therapeutic option to reduce appetite and weight, and is hence a promising preventive option.

Methods and participants: This is a 24-week parallel, double-blind, multicenter, randomized, placebo controlled superiority trial investing the GLP-1 analogue dulaglutide to prevent antipsychotic induced weight gain. Patients will be randomized 1:1 by blocks of 4 and 6, stratified by site and medication, with a computer-generated randomization sequence. A total of 154 participants will be recruited (77 in each arm).

Intervention and outcome: Eligible patients will receive dulaglutide (0.75mg/week) or placebo subcutaneously once weekly for 24 weeks. A follow-up assessment will be performed 12 months after inclusion. The primary outcome is mean weight change after 24 weeks calculated as ratio of the initial weight and will be treated as a continuous variable.

Discussion: This will be the first double blind randomized controlled trial investigating the prevention of weight gain in patients receiving SGAs using the GLP-1 analogue dulaglutide. A reduction in weight gain under SGAs could contribute to well-being, long-time adherence and overall therapeutic success of patients suffering from a schizophrenia spectrum disorder.