Does semaglutide improve quality of life for adults with schizophrenia and prediabetes?

Semaglutide, a GLP-1 receptor agonist, is known for weight loss and blood sugar control. For adults with schizophrenia and prediabetes, a key question is whether it also improves quality of life. A 2025 randomized trial found that semaglutide improved physical quality of life over 30 weeks, but did not significantly affect mental quality of life or psychiatric symptoms ⁵⁹¹⁰.

What the research says

A 2025 randomized clinical trial (the HISTORI trial) tested semaglutide in 154 adults with schizophrenia, prediabetes, and overweight or obesity ⁹. Participants received once-weekly semaglutide (up to 1.0 mg) or placebo for 30 weeks ⁹. Secondary analyses from this trial showed that semaglutide improved the Physical Component Summary score of the SF-36v2 quality-of-life questionnaire at weeks 15 and 30, with effects exceeding the minimally important difference ⁵¹⁰. About half of this improvement was linked to weight loss, though the indirect effect through weight loss was not statistically significant ⁵¹⁰. However, semaglutide did not improve the Mental Component Summary score or psychiatric symptoms measured by the PANSS-6 scale ⁵¹⁰. These findings suggest that the quality-of-life benefit is primarily physical, likely due to weight reduction and metabolic improvements.

What to ask your doctor

• Could semaglutide help improve my physical quality of life, even if it doesn't directly affect my psychiatric symptoms?
• What are the potential side effects of semaglutide, especially when taken with my current antipsychotic medications?
• How does semaglutide compare to other treatments for prediabetes and weight management in people with schizophrenia?
• Would I need to monitor my blood sugar or other metabolic markers while on semaglutide?
• Is a 30-week trial enough to see lasting benefits, or would I need longer treatment?