TREATMENT with glucagon-like peptide-1 receptor agonists (GLP-1RAs) may reduce the risk of dementia and Alzheimer’s disease in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM), according to a new retrospective cohort study.
Patients with CKD and T2DM face a heightened risk of cognitive decline, driven by vascular dysfunction, insulin resistance, and chronic inflammation. While GLP-1RAs are widely used for glycaemic control and have demonstrated cardiovascular and renal benefits, emerging evidence suggests they may also exert neuroprotective effects. However, their impact on dementia risk in patients with more advanced CKD has remained unclear.
To address this, researchers analysed electronic health record data from the TriNetX global research network, incorporating 67 healthcare organisations across the USA. The investigators identified adults with CKD stage 3 or later and T2DM who were newly prescribed either a GLP-1RA or a dipeptidyl peptidase-4 inhibitor (DPP4i) between January 2015 and December 2020. Patients with prior exposure to either drug class, a recent dementia diagnosis, or recent hospitalisation were excluded.
CKD Dementia Risk: Significant Reduction with GLP-1 Therapy
The primary outcome was incident dementia over a follow-up period ranging from 90 days to five years. Specific subtypes assessed included Alzheimer’s disease, vascular dementia, frontotemporal dementia, Parkinson’s disease, extrapyramidal and movement disorders, and dementia with Lewy bodies. Time-to-event analyses were conducted using Kaplan–Meier curves and Cox proportional hazards models.
Compared with DPP4i use, GLP-1RA therapy was associated with a 20% lower risk of overall dementia (hazard ratio [HR] 0.80; 95% CI 0.71–0.91; p=0.001). The risk of Alzheimer’s disease was reduced by 24% (HR 0.76; 95% CI 0.59–0.98; p=0.033). No statistically significant differences were observed for other neurodegenerative outcomes, including vascular dementia or Parkinson’s disease.
Implications for Diabetes Management
The authors suggest that GLP-1RAs may confer neuroprotective benefits beyond glycaemic control in this high-risk population. While the observational design limits causal inference, the findings add to growing evidence supporting pleiotropic effects of GLP-1–based therapies. Further prospective studies are needed to confirm these associations and clarify optimal treatment strategies for patients with CKD and diabetes at risk of cognitive decline.
Reference
Lee WT et al. GLP-1 receptor agonists reduce dementia and Alzheimer disease risk in diabetic patients with CKD. NDT. 2026;doi: 10.1093/ndt/gfag032.
