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

BACKGROUND: 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 GLP-1 receptor agonists (RAs) on cognitive measures in persons with cognitive impairment and T2DM from available systematic reviews and meta-analyses.

METHODS: We conducted a literature search on 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.). Nine meta-analyses examining the effect of GLP-1 RAs on cognitive function in adults with T2DM were included. Primary research studies examining race, sex, children, animals and neurodegenerative diseases other than AD were excluded.

RESULTS: Nine systematic reviews and meta-analyses support that there is convergence and replication of findings insofar as data support the hypothesis that GLP-1 RAs are associated with a reduction in overall cognitive decline in adults with T2DM and dementia/AD. Various meta-analyses indicated that GLP-1 RAs had improved results on cognitive assessments (total learning; p = 0.039; p < 0.00001). Some meta-analyses observed a change in cognition but lacked sufficient statistical significance (p > 0.05). More studies are needed to determine definitive clinical significance.

CONCLUSIONS: We report that 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.