Semaglutide helps overweight schizophrenia patients on clozapine lose weight safely

For patients with schizophrenia being treated with clozapine who have high BMI, semaglutide delivers weight-loss benefits without affecting psychotic symptoms or altering clozapine concentrations, according to the double-blind, phase II COaST study.

COaST included 31 adults (mean age 38.9 years, 67.7 percent male, 84 percent White) with schizophrenia or schizoaffective disorder, who had received a prescription for clozapine for at least 18 weeks, had a BMI of at least 26 kg/m², and had less than 5 percent bodyweight increase or loss in the previous 3 months.

The participants were randomly assigned to receive once-weekly subcutaneous semaglutide titrated to 2.0 mg (n=15) or placebo (n=16) for 36 weeks. Recruitment was suspended before achieving the intended number of 80 participants due to nonavailability of the investigational product.

The primary outcome was percentage body weight change at 36 weeks. Secondary outcomes included clozapine and norclozapine concentrations as well as psychosis symptoms as measured by the Positive and Negative Syndrome Scale (PANSS).

At week 36, the semaglutide group had a significantly greater weight loss compared with the placebo group (–13.88 percent vs 0.42 percent; between-group difference, –13.46 percent; p<0.0001). No significant between-group differences were seen in clozapine or norclozapine concentrations and PANSS scores.

In terms of safety, semaglutide was well-tolerated. None of the participants in either treatment group experienced serious adverse events that were deemed to be related to the treatment. The incidence of constipation was low.