Liraglutide and the management of overweight and obesity in people with schizophrenia, schizoaffective disorder and first-episode psychosis: protocol for a pilot trial

Abstract

BackgroundPeople with severe mental illness (SMI) are two to three times more likely to be overweight and obese than the general population and this is associated with significant morbidity and premature mortality. Although lifestyle interventions can support people with SMI to lose weight, some are unable to make the necessary lifestyle changes or, despite making the changes, continue to gain weight.ObjectiveTo assess the feasibility and acceptability of delivering a full-scale trial evaluating whether liraglutide 3.0 mg, a once-daily injectable therapy, may be an effective treatment of overweight and obesity in people with schizophrenia, schizoaffective disorder and first-episode psychosis.MethodsDesign: a single-centre, double-blind, randomised, placebo-controlled trial.Setting: mental health facilities within Southern Health NHS Trust.Participants: 60 adults with schizophrenia, schizoaffective or first-episode psychosis prescribed antipsychotic medication will be recruited. Participants will be overweight or obese, defined by their baseline BMI which will be:• BMI ≥ 30 kg/m2 or• BMI ≥ 27 kg/m2 to < 30 kg/m2 in the presence of at least one weight-related consequence.This is in concordance with the current EU licence for liraglutide (maximum dosage 3.0 mg).Intervention: participants will be allocated in a 1:1 ratio using a computer-based randomisation programme to either once-daily subcutaneously administered liraglutide or placebo, titrated to 3.0 mg daily, for 6 months. All participants will receive standardised written information about healthy eating and exercise at their randomisation visit.Outcomes: the main aim of the study is to gather data on recruitment, consent, retention and adherence. Qualitative interviews with a purposive sub-sample of participants and healthcare workers will provide data on intervention feasibility and acceptability. Secondary clinical outcome measurements will be assessed at 3 and 6 months and will include: weight, fasting plasma glucose, lipid profile, HbA1c level; and the Brief Psychiatric Rating Scale.DiscussionThis study should provide evidence of the potential benefits of liraglutide (maximum dosage 3.0 mg daily) on body weight and metabolic variables in people with schizophrenia, schizoaffective disorder and first-episode psychosis. It will also address the feasibility and acceptability of the use of liraglutide in mental health settings. This will inform the design of a longer outcome study that will be needed to determine whether any weight loss can be maintained in the long term.Trial registrationUniversal Trial Number (UTN), ID: U1111-1203-0068. Registered on on 2/10/2017.European Clinical Trials Database (EudraCT), ID: 2017-004064-35. Registered on 3/10/2017.Electronic supplementary materialThe online version of this article (10.1186/s13063-019-3689-5) contains supplementary material, which is available to authorized users.

Liraglutide and the management of overweight and obesity in people with severe mental illness: qualitative sub-study

“…These studies, however, used the doses used to treat diabetes. We therefore undertook a pilot feasibility to compare the use of liraglutide (maximum dose 3.0 mg daily) with placebo in obese or overweight people with schizophrenia, schizoaffective disorder or first episode psychosis [8,9]. This study demonstrated that although recruitment was challenging, once participants were enrolled, retention and adherence to the trial medication was similar to previous studies of liraglutide 3 mg daily in the general population.…”

The use of liraglutide 3.0 mg daily in the management of overweight and obesity in people with schizophrenia, schizoaffective disorder and first episode psychosis: Results of a pilot randomized, double‐blind, placebo‐controlled trial

“…The study protocol for this trial has been published previously 17 . In brief, we conducted a double‐blind, randomized, controlled pilot trial from 24 July 2018 (first patient, first visit) to 5 May 2020 (last patient, last visit) in mental health centres and primary care in Southern Health NHS Foundation Trust, UK (Figure 1).…”

“…pancreatitis or an estimated glomerular filtration rate of less than 30 mL/min/1.73m 2 ), use of other pharmacological products for weight management, substance abuse or suboptimally managed diabetes defined by an HbA1c greater than 8% (>64 mmol/mol). A complete list of inclusion and exclusion criteria is available in Appendix S1 17 …”

Anti-stress effects of the glucagon-like peptide-1 receptor agonist liraglutide in zebrafish

“…Liraglutide has 97% homology to the human GLP-1 and was approved by the FDA in 2010. Like other GLP-1R agonists, it stimulates insulin secretion and inhibits glucagon release by the pancreas, delays gastric emptying, and reduces appetite (LIM et al, 2009;LÓPEZ-FERRERAS et al, 2018;MOJSOV, 2000;WHICHER et al, 2019). Due to its weight loss properties, liraglutide was repurposed by the Food and Drug Administration (FDA) in 2014 as a treatment for obesity.…”