Could GLP-1s help with cognitive symptoms, pychosis of schizophrenia?

Glucagon-like peptide 1 (GLP-1) drugs, such as semaglutide and liraglutide, are prescribed to treatment Type 2 diabetes and obesity. They work to treat those conditions in a variety of ways, modifying insulin secretion and delaying gastric emptying. But there are GLP-1 receptors in the brain, too, including in the amygdala, hippocampus and nucleus accumbens, regions of the brain that play a role in governing mood, stress and mental responses to rewards. Moreover, some preclinical studies have shown that GLP-1s influence the activity of the hypothalamic-pituitary-adrenal (HPA) axis and dopaminergic neurotransmission. All of this evidence points to the plausibility of GLP-1s having an effect on mental conditions and, pending more research, possibly being used for treatment.

That tantalizing prospect led lead and corresponding author Brianna Sa, a medical student at the University of Miami Miller School of Medicine, and her colleagues, most of them also at the Miami medical school, to conduct a comprehensive literature review of studies of GLP-1s and psychiatric outcomes. Searching on Google Scholar and in PubMed, Sa and her colleagues initially identified 318 studies using expansive criteria that included randomized controlled trials, observational studies, and meta-analyses that had primary and secondary outcomes of interest. But after applying various exclusion criteria, they ended up with 38 studies in their review.

Along with depression, anxiety disorders and eating disorders, Sa and her colleagues considered studies of the schizophrenia spectrum and other psychotic disorders. They noted that GLP-1s have been studied in people with schizophrenia mainly for their metabolic effects. Hope of cognitive and antipsychotic effects has been seeded by the preclinical findings of dopaminergic modulation signaling. They cite research showing that exenatide did not significantly improve cognitive performance in people with schizophrenia in a 12-week randomized clinical trial.Brand-name exenatide was marketed under the names Bydureon Cise and Byetta, but they are no longer on the market.

Sa and her colleagues also note, though, that meta-analyses show that GLP-1s do not exacerbate psychotic symptoms. They cite studies showing no change in psychopathologic severity among people taking exenatide or liraglutide, which is sold under the brand name Victoza as a treatment for Type 2 diabetes and Saxenda as a treatment for obesity. They also cite findings from a small study (62 study subjects total) published last year that compared semaglutide and metformin with metformin alone as a treatment for weight gain related to antipsychotics among people with Type 2 diabetes. Semaglutide is sold as Ozempic for Type 2 diabetes and as Wegovy for weight loss. The results showed no adverse psychiatric events among the patients taking both semaglutide and metformin. Findings from another small study, published in 2024, comparing semaglutide to metformin found that patients taking semaglutide experienced an improvement in their quality of life and a reduction in psychiatric symptoms.

So what’s the verdict on GLP-1s and schizophrenia spectrum and other psychotic disorders? Sa and her colleagues don’t arrive at a firm conclusion. Animal studies suggest that there might be cognitive benefit and amelioration of psychotic symptoms, they write in the discussion section of the paper, but “these effects have not been consistently replicated in human studies.” Cognitive benefits may not translate to the “complex neurobiology of chronic schizophrenia,” they note.

Sa and her colleagues say that further research is needed to tease apart whether the benefits from GLP-1s among people with schizophrenia are the result of “direct neuropsychotropic effects” or indirect benefits from their metabolic and anti-inflammatory effects.

The review was published on a full-text open access basis in the January 2026 issue of the journal Diabetes, Obesity and Metabolism. It had been previously published online late last year.