by Sanjukta Mondal, Medical Xpress
edited by Sadie Harley, reviewed by Robert Egan
Semaglutide significantly improved glycemic control and weight outcomes in individuals with schizophrenia spectrum disorders. Credit: pxhere.com/en/photo/1375343
Semaglutide medications like Ozempic and Wegovy can help lower the risk of heart and metabolic diseases in people with schizophrenia spectrum disorders, according to a study published in JAMA Psychiatry.
Glucagon-like peptide–1 receptor agonist (GLP-1RAs) drugs, such as semaglutide, mimic the natural gut hormone GLP-1 that regulates hunger and food intake. By activating GLP-1 receptors in the brain, the drug reduces hunger and slows gastric emptying, helping one feel full longer. It also enhances glucose-dependent insulin secretion, thereby improving blood sugar control.
Researchers in Denmark recruited 73 adults taking antipsychotic medications who were showing early signs of diabetes and had an average BMI of 36, which falls in the category of obesity. The participants, aged 18 to 65 years, were randomly assigned to receive either weekly semaglutide injections or a placebo for 6.5 months.
This double-blind, placebo-controlled randomized clinical trial was conducted at three sites in Denmark, where neither participants nor researchers knew who received which treatment until the study concluded.
After the treatment period, nearly half of participants receiving semaglutide reached HbA1c levels below 5.4%, showing improved blood sugar control. They also lost an average of 9.2 kg more than those taking the placebo.
These results are encouraging since the patients who take second-generation antipsychotics (SGAs) such as clozapine or olanzapine for managing schizophrenia are vulnerable to metabolic and cardiovascular diseases.
Studies have found that people on SGAs have a two to three times higher risk of dying early and a life expectancy of 15 years less than the general population, as they develop heart disease, obesity, and type 2 diabetes. These side effects start appearing within a short time after the medication is started.
Effects on glycemia and body composition measures. Credit: JAMA Psychiatry (2025). DOI: 10.1001/jamapsychiatry.2025.3639
Attempts to manage these side effects through medication changes or lifestyle adjustments often don’t help, and in many cases, switching antipsychotics can actually make psychiatric symptoms worse.
In contrast, the low-dose semaglutide treatment regimen followed in this new study not only led to positive metabolic benefits but also did so without worsening the psychiatric symptoms.
Early intervention and its effects
The researchers in this study were curious whether early intervention could prevent or reduce long-term heart and metabolic damage. So they designed the study to focus on participants who had started clozapine or olanzapine within the past five years and were showing early signs of blood sugar problems (HbA1c between 5.4% and 7.4%) but were not on any diabetes medications.
In addition to their antipsychotic medication, participants in the semaglutide group started with 0.25 mg once weekly at the beginning of the study, gradually increasing to 1 mg by week eight to help their bodies adjust to the treatment. The commonly reported side effects by this group were gastrointestinal issues like nausea and vomiting, which, for most participants, were rather mild and temporary.
Sixteen people (eight from each group) did not complete the 26-week trial, but among those who did, the difference between those who received the medication and those on a placebo was striking. 43% of participants achieved healthy blood sugar levels compared to just 3% in the placebo group.
Those on semaglutide also trimmed 7.0 cm (3 inches) off their waistlines and lost 6.1 kg (13 pounds) of body fat. The smokers in the semaglutide group also reported feeling less dependent on nicotine.
The researchers highlighted that these findings support the use of GLP-1RAs as a potential early intervention strategy to reduce cardiometabolic risk in this vulnerable population.
They call for longer studies with larger sample sizes to confirm these results and see whether starting GLP-1 drugs early could also improve heart health and reduce addictive behaviors.
Written for you by our author Sanjukta Mondal, edited by Sadie Harley, and fact-checked and reviewed by Robert Egan—this article is the result of careful human work. We rely on readers like you to keep independent science journalism alive. If this reporting matters to you, please consider a donation (especially monthly). You’ll get an ad-free account as a thank-you.
More information: Marie R. Sass et al, Semaglutide and Early-Stage Metabolic Abnormalities in Individuals With Schizophrenia Spectrum Disorders, JAMA Psychiatry (2025). DOI: 10.1001/jamapsychiatry.2025.3639
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