New clinical evidence suggests that the diabetes and obesity medication Semaglutide may help reverse the metabolic side-effects commonly experienced by patients taking second-generation antipsychotics, often prescribed for schizophrenia and related disorders.
People diagnosed with schizophrenia typically face a noticeably reduced life expectancy compared with the general population , on average about 15 years shorter. Significantly, physical health issues such as obesity, type 2 diabetes and cardiovascular disease , rather than the psychiatric condition itself , account for much of this excess mortality.
Antipsychotic medications , especially drugs such as Clozapine and Olanzapine , while effective in controlling psychosis, frequently cause rapid weight gain and disturbances in glucose metabolism. These side effects can lead to pre-diabetes, full-blown type 2 diabetes and increased cardiovascular risk, creating a difficult situation for both patients and clinicians. Discontinuing these medications may risk relapse of psychosis; conventional add-on treatments such as Metformin or Topiramate often bring only modest benefits.
Hence there is a pressing need for effective interventions that manage metabolic harm without undermining mental-health stability.
A new randomised, double-blind, placebo-controlled clinical trial , led by researchers at the Mental Health Center Copenhagen and involving collaborators from Denmark and the US , tested whether semaglutide could protect patients receiving clozapine or olanzapine from early metabolic deterioration.
The study enrolled 73 adult participants with schizophrenia-spectrum disorders, all of whom had begun treatment with clozapine or olanzapine within the previous five years and showed signs of pre-diabetes or early-stage diabetes. Participants were randomly assigned to one of two groups: one receiving a weekly injection of semaglutide (gradually increased to 1 mg) and another receiving a placebo. The trial lasted 26 weeks.
At the end of the period, semaglutide recipients showed significantly better metabolic outcomes: HbA1c, a measure of long-term blood sugar control, fell by 0.25 percentage points on average compared with placebo (95% CI: –0.33 to –0.16; P < 0.001).
Crucially, 43 % of those on semaglutide achieved “low-risk” HbA1c levels (< 5.4%), compared with just 3 % of the placebo group.
Patients lost on average 9.2 kg in body weight (≈ 20 lb) , accompanied by a reduction in waist circumference of around 7 cm.
Body composition analysis revealed the weight loss was due to a reduction in fat mass rather than muscle, a favourable outcome for overall health.
In terms of safety and adaptability, there was no deterioration of psychiatric symptoms in the semaglutide group, and hospitalisation rates for psychiatric reasons were similar in both arms of the trial. Gastrointestinal side-effects (such as nausea, vomiting and constipation) were more common among those receiving semaglutide, but these are well-known effects of the drug class and often mild or transient.
One participant in the semaglutide group died of sudden cardiac death shortly after the trial ended , but an autopsy found no link to the study drug.Secondly-line measures including lipid profile, liver function and blood pressure showed no substantial change.
Although the trial was carried out in Denmark and the US, the findings may have relevance , where antipsychotic-related weight gain and diabetes risk are also major concerns. The idea of using a once-weekly GLP-1 receptor agonist such as semaglutide to counteract metabolic harm could , if validated in larger, longer-term, and more diverse populations , offer psychiatrists a new tool to safeguard the physical health of patients with severe mental illness.
In the context of the public health system, preventing the onset of diabetes or reducing obesity-related complications could also yield long-term cost savings, and reduce the cardiovascular burden borne by people with severe mental illness.
The authors themselves point out several limitations. The trial ran for only 26 weeks, a relatively short timeframe given the chronic nature of schizophrenia and long-term cardiometabolic risk. The dose used (1 mg weekly) was lower than the 2.4 mg often used in obesity treatment; higher doses might yield larger benefits, but may also carry more risk.
Additionally, the majority of participants were White, limiting the generalisability of the results to other ethnic groups, who may have different metabolic risk profiles.
Finally, the practicalities , such as cost, access, and whether health services would adopt such a therapy , remain uncertain.
The trial, titled “Semaglutide and Early-Stage Metabolic Abnormalities in Individuals With Schizophrenia Spectrum Disorders,” has opened the door to a potentially powerful new strategy. As more research unfolds, semaglutide , originally developed for type 2 diabetes and obesity , may become a valuable adjunct treatment in psychiatry, helping bridge the gap between mental-health care and physical-health outcomes.
Sources:
- “Semaglutide helps manage metabolic side-effects of antipsychotic drugs,” PsyPost, December 9, 2025. PsyPost – Psychology News
- Sass MR, Klausen MK, Schwarz CR, et al. “Semaglutide and Early-Stage Metabolic Abnormalities in Individuals With Schizophrenia Spectrum Disorders: A Randomized Clinical Trial.” JAMA Psychiatry, 2025. JAMA Network
- “Semaglutide Helps Counter Antipsychotic-Related Metabolic Risks,” Medical Dialogues, December 2025. Medical Dialogues
