Semaglutide in Schizophrenia: A Step Forward in Managing Metabolic Health?

Semaglutide in Schizophrenia: A Step Forward in Managing Metabolic Health?

Managing schizophrenia often extends well beyond controlling psychiatric symptoms. Weight gain and metabolic complications can become equally important concerns, particularly for people receiving clozapine. While clozapine remains one of our most effective treatments for treatment-resistant schizophrenia, its metabolic adverse effects can significantly affect long-term physical health.

This is where semaglutide may have a role to play.

Recent clinical trials have shown encouraging results. In the phase 2 COaST trial, people with schizophrenia on clozapine and living with obesity experienced a mean body-weight reduction of 13.9% over 36 weeks with semaglutide compared with placebo. Reassuringly, clozapine concentrations remained unchanged, and no serious adverse events were attributed to semaglutide.

Similarly, another randomised trial involving individuals with schizophrenia-spectrum disorders and early metabolic abnormalities reported an average weight loss of approximately 4.7 kg, or 4.4% of body weight, over 16 weeks. Benefits extended beyond weight reduction, with improvements in waist circumference, systolic blood pressure, triglycerides, and HbA1c.

However, there is an important clinical caveat. Clozapine is already associated with gastrointestinal hypomotility and constipation, and GLP-1 receptor agonists can further slow gastrointestinal motility. When the two are used together, careful monitoring becomes particularly important.

In practice, a cautious “start low and go slow” approach may be helpful. Regularly asking about bowel habits, identifying constipation early, and incorporating preventive measures such as adequate hydration, fibre intake, physical activity, and laxatives when indicated can make treatment safer.

Semaglutide therefore represents a promising option for addressing metabolic health in schizophrenia. Its use, however, is best viewed as part of comprehensive care-balancing psychiatric stability with physical health, careful monitoring, and individualised clinical decision-making.