Lancet Pschiatry

Semaglutide effective for weight loss in small trial of patients with schizophrenia on clozapine

July 16, 2025

Semaglutide resulted in significantly greater weight loss vs. placebo—without detriment to psychosis symptoms or clozapine concentrations—in this small, randomized trial.

Study. The COaST Australian multi-site placebo-controlled trial involved 31 adults (age range, 21–58 years; 21 male; 84% White, others were of Asian, Aboriginal, Maori, Indian, or Pacific Island descent) with schizophrenia or schizoaffective disorder and BMI ≥26 kg/m². Patients were randomized to semaglutide titrated to 2.0 mg SC once a week vs. placebo, for 36 weeks. Primary outcome: % body-weight change. Secondary outcomes: Positive and Negative Syndrome Scale (PANSS) psychosis symptoms, clozapine and norclozapine concentrations.

Results. Semaglutide resulted in a 13.88% reduction in body weight vs. 0.42% with placebo (between-group difference: –13.46%; p<0.0001) at week 36. No differences were noted in PANSS scores or concentrations of clozapine or norclozapine. The drug was well tolerated; no serious treatment-related adverse events were noted, and rates of constipation were low.

Source:

Siskind D, et al. (2025, July). Lancet Psychiatry. 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. https://pubmed.ncbi.nlm.nih.gov/40506208/