The effect of glucagon-like peptide 1 (GLP-1) receptor agonists on cognition: A systematic review of systematic reviews and meta-analyses.

BACKGROUND: Results from extant studies indicate that type 2 diabetes mellitus (T2DM) is associated with decreased cognitive function and increased risk for dementia, notably Alzheimer's Disease (AD). Herein, we aimed to evaluate the effect of glucacon-like peptide-1 receptor agonists (GLP-1 RAs) on cognitive measures in persons with cognitive impairment and T2DM from available systematic reviews and meta-analyses. METHODS: A literature search was conducted using Web of Science and MEDLINE from inception to July 15, 2025. Article screening and data extraction were conducted by three reviewers (H.B., C.D., S.L.). Primary research studies examining race, sex, children, animals and neurodegenerative diseases other than AD were excluded. RESULTS: Nine systematic reviews and meta-analyses examining the effect of GLP-1 RAs on cognitive function in adults with T2DM were included. Evidence suggests that GLP-1 RAs are associated with a reduction in overall cognitive decline in adults with T2DM and dementia/AD. Replicated findings from meta-analyses indicated that GLP-1 RAs improved performance on cognitive assessments (total learning; p = 0.039; p < 0.00001). Some meta-analyses observed a change in cognitive measures but lacked sufficient statistical significance (p > 0.05). CONCLUSIONS: GLP-1 RAs positively affect cognitive function in AD patients with T2DM. However, their efficacy on disparate cognitive domains requires further replication in larger scale controlled clinical trials.