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

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. 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. 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. 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. • Cognition is negatively affected by type 2 diabetes, particularly Alzheimer's disease. • We aimed to determine the effects of GLP-1 RA's, on cognitive function. • We performed an extensive literature search to extract meta-analyses on the topic. • Found that GLP-1 RA's have a positive impact on Alzheimer's cognition • Further replication in larger clinical trials is needed to test accurate effects.