| Title: |
Efficacy and safety of semaglutide versus placebo for people with schizophrenia on clozapine with obesity (COaST): a phase 2, multi-centre, participant and investigator- blinded, randomised controlled trial in Australia |
| Authors: |
Siskind, D; Baker, A; Arnautovska, U; Warren, N; Russell, A; DeMonte, V; Halstead, S; Iyer, R; Korman, N; McKeon, G; Medland, S; Parker, S; Stedman, T; Trott, M |
| Publisher Information: |
Elsevier |
| Publication Year: |
2025 |
| Collection: |
Griffith University: Griffith Research Online |
| Description: |
Background: People with schizophrenia have a 16–20-year reduction in life expectancy, primarily due to cardiometabolic disease. Clozapine, the most efficacious antipsychotic for treatment-resistant schizophrenia, is associated with weight gain and metabolic dysfunction. Glucagon-like peptide-1 receptor agonists, including semaglutide, contribute to substantial weight loss in the general population, but their effect and safety profile in people with schizophrenia remain unknown. We evaluated the efficacy and safety of semaglutide for weight reduction in individuals with schizophrenia who were prescribed clozapine. Methods: COaST was an Australian randomised, placebo-controlled, multi-site trial, independent of pharmaceutical industry support, with methods informed by people with lived experience. Adults (aged 18–64 years) across six sites were randomly assigned (1:1) to once weekly subcutaneous semaglutide titrated to 2·0 mg or placebo for 36 weeks. Participants were included if they fulfilled criteria for schizophrenia or schizoaffective disorder, were prescribed clozapine for 18 weeks or more, had a BMI of at least 26 kg/m 2 , and had less than 5% bodyweight increase or loss in the previous 3 months. The primary outcome was percentage body weight change, analysed using a mixed model for repeated measures, at 36 weeks post-baseline assessment. All investigators and participants were masked to medication allocation. Secondary measures included clozapine and norclozapine concentrations and psychosis symptoms as measured by the Positive and Negative Syndrome Scale (PANSS). The protocol was prospectively registered with the Australia New Zealand Clinical Trials Registry (ACTRN12621001539820; recruitment finished, pending follow-up assessments). Findings: 166 individuals were screened for eligibility, 135 were excluded, and the remaining 31 were randomly assigned to either the semaglutide group (n=15) or the control group (n=16). 21 males and ten females were included in the study, with a mean age of 38·9 years ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
Lancet Psychiatry; Siskind, D; Baker, A; Arnautovska, U; Warren, N; Russell, A; DeMonte, V; Halstead, S; Iyer, R; Korman, N; McKeon, G; Medland, S; Parker, S; Stedman, T; Trott, M, Efficacy and safety of semaglutide versus placebo for people with schizophrenia on clozapine with obesity (COaST): a phase 2, multi-centre, participant and investigator- blinded, randomised controlled trial in Australia, Lancet Psychiatry, 2025, 12 (7), pp. 493-503; https://hdl.handle.net/10072/438504 |
| DOI: |
10.1016/S2215-0366(25)00129-4 |
| Availability: |
https://hdl.handle.net/10072/438504; https://doi.org/10.1016/S2215-0366(25)00129-4 |
| Rights: |
open access |
| Accession Number: |
edsbas.6C05FDF7 |
| Database: |
BASE |