Study wrapper · #299
Weight loss and gut microbial changes associated with semaglutide among people living with schizophrenia receiving clozapine or olanzapine: An open-label 24-week semaglutide intervention and 76-week trial.
Editor's note
A small, open-label, single-arm intervention (n=26; 17 completers) in a real-world mental-health setting — a design with no control group, so results cannot be separated from other influences. Over 24 weeks of nurse-administered semaglutide, adults with schizophrenia on clozapine or olanzapine lost a mean 9.8% of body weight (about 10 kg), with reduced waist circumference and a non-significant HbA1c change; gut microbial diversity fell over time. At 76 weeks — one year after stopping — mean weight loss had attenuated to 5.1%, consistent with the regain seen when GLP-1 agonists are discontinued. This addresses a genuinely important, under-served population where antipsychotic-associated weight gain is a major problem, and the weight findings align with semaglutide's large Phase 3 record. But the absence of a control arm, the small sample and notable dropout limit confidence, and the microbiome findings are exploratory. These are reported associations, not proof of benefit specific to this group; a controlled trial would be needed to confirm them.
Plain-language abstract
People with schizophrenia who take antipsychotics like clozapine or olanzapine often gain substantial weight. This study tested whether semaglutide could help. In a public mental-health clinic, 26 adults with schizophrenia (but not diabetes) and a BMI over 27 received weekly semaglutide injections given by a nurse for 24 weeks, after a gradual dose build-up, with no comparison group. Their stool was sampled to track gut bacteria. On average, participants lost about 9.8% of their body weight (roughly 10 kg) and reduced their waistline by about 7% over 24 weeks; a blood-sugar marker (HbA1c) dropped slightly but not significantly. The variety of gut bacteria decreased the longer people stayed on the drug. About two-thirds finished the 24-week phase. A year after stopping treatment (76 weeks total), average weight loss had shrunk to about 5%, meaning some weight came back once the drug stopped. The authors report that semaglutide was linked to meaningful weight loss in this group but note the benefits faded after discontinuation. Because there was no control group and the study was small, the results are preliminary.