Semaglutide Linked to Fewer Cognitive Symptoms in Psychiatric Disorders

Key Clinical Summary

• In a retrospective US cohort of 13,007 adults with psychiatric diagnoses, semaglutide initiation was associated with fewer clinician-recorded cognitive signs and symptoms over 12 months compared with no antidiabetic treatment, glipizide, and empagliflozin.
• Cognitive symptom scores were lower with semaglutide than with sitagliptin, but the difference was not statistically significant.
• Associations were strongest for memory and broader cognitive function, and were most consistently observed among patients with major depressive disorder (MDD).

Semaglutide initiation was associated with fewer clinician-recorded cognitive signs and symptoms among adults with psychiatric disorders compared with several antidiabetic treatment groups, according to findings presented in a poster at the 2026 Psych Congress. The association was particularly evident for memory and broader cognitive function and was most consistently observed in patients with MDD.

Study Findings

Researchers conducted a retrospective cohort study using de-identified electronic health records from the NeuroBlu Data V25R3 database spanning 1999 to 2024. The analysis included adults with any psychiatric diagnosis who had at least 1 clinician-rated cognitive assessment during the 12 months before and after initiation of an antidiabetic medication.

The study included 13,007 adults with a mean age of 62.0 years; 48.4% were female. Of these, 1261 were prescribed semaglutide. Investigators compared semaglutide initiation with sitagliptin, empagliflozin, glipizide, or no antidiabetic treatment.

The primary outcome was a 0 to 100-point composite cognitive signs and symptoms score over 12 months. Analyses were adjusted for baseline cognitive score and prespecified covariates.

Mean 12-month cognitive symptom scores were lower with semaglutide (11.14) than with no treatment (14.91; mean ratio [MR], 0.75; 95% CI, 0.65-0.85), glipizide (13.46; MR, 0.83; 95% CI, 0.70-0.93), and empagliflozin (13.69; MR, 0.81; 95% CI, 0.69-0.94).

Scores were also numerically lower with semaglutide than with sitagliptin (12.52; MR, 0.89; 95% CI, 0.77-1.02), but the difference was not statistically significant.

Clinical Implications

Cognitive signs and symptoms are common across psychiatric disorders and can be challenging to treat. In this study, semaglutide initiation was associated with fewer cognitive signs and symptoms over 12 months compared with several comparator groups, with the strongest associations observed for memory and broader cognitive function.

Disorder-specific analyses showed that the associations were most consistently observed in patients with MDD. However, the retrospective observational design does not establish that semaglutide caused the differences in cognitive symptoms.

The findings, therefore, should not be interpreted as evidence supporting semaglutide as a treatment for cognitive symptoms in psychiatric disorders. Instead, they identify an association that warrants prospective investigation to determine whether GLP-1 receptor agonist treatment has clinically meaningful cognitive effects in psychiatric populations.

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Reference
Lipunova N. Cognitive signs and symptoms in people with a psychiatric diagnosis on semaglutide: a retrospective cohort study of 13,007 patients in the United States. Poster presented at Psych Congress, 15-21, 2026; New Orleans, Louisiana.