GLP-1RA significantly reduces dementia and cognitive impairment in diabetic patients: JAMA

A new study published in the Journal of American Medical Association showed that glucagon-like peptide-1 receptor agonists (GLP-1RAs)-based glucose-lowering treatment was linked to reduction in dementia or cognitive impairment.

A risk factor for dementia, diabetes is thought to be responsible for around 5% of the population-attributable percentage of dementia cases. Also, diabetes increases the incidence of ischemic stroke, which may function as a mediator in the relationship between diabetes and vascular dementia.

The effectiveness of glucose-lowering medication in preventing incident dementia is unknown, despite the knowledge that diabetes is a risk factor for dementia. Thus, to ascertain whether cardioprotective glucose-lowering therapy (sodium-glucose cotransporter-2 inhibitors (SGLT2is), GLP-1RAs, metformin, and pioglitazone) was linked to a lower risk of dementia or cognitive impairment, as well as among the primary dementia subtypes, this study was carried out.

Studies published between the database's creation and July 11, 2024, were found by searching the PubMed and Embase databases. This study shortlisted randomized clinical trials that compared cardioprotective glucose-lowering treatment with controls who reported dementia or a change in cognitive scores.

Based on data from phase III randomized clinical studies, medication classes that are suggested by recommendations for decreasing cardiovascular events were referred to as cardioprotective glucose-lowering treatments. Independent evaluations of the inclusion criteria were conducted, and disagreements were settled by consensus. 

12 trials evaluating SGLT2is, 10 trials evaluating GLP-1RAs, and 1 trial evaluating pioglitazone (no trials of metformin were found) were among the 26 randomized clinical trials (N = 1,64,531 participants) that reported the incidence of dementia or cognitive impairment. The mean (SD) age of the trial participants was 64.4 (3.5) years, and 57,470 (34.9%) of them were female.

Overall, there was no significant correlation seen between cardioprotective glucose-lowering medication and a decrease in dementia or cognitive impairment. GLP-1RAs, but not SGLT2is, were linked to a statistically significant decrease in dementia all medication classes. Overall, this meta-analysis revealed that glucose lowering with GLP-1RAs reduced all-cause dementia, even if cardioprotective glucose-lowering treatments were not linked to an overall decrease in the same.

Source:

Seminer, A., Mulihano, A., O’Brien, C., Krewer, F., Costello, M., Judge, C., O’Donnell, M., & Reddin, C. (2025). Cardioprotective glucose-lowering agents and dementia risk: A systematic review and meta-analysis: A systematic review and meta-analysis. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2025.0360