Abstract: TH-PO0364
GLP-1 Receptor Agonists Reduce Dementia and Alzheimer Disease Risk in Patients with Diabetes and Advanced CKD: Real-World Evidence from TriNetX
Session Information
- Diabetic Kidney Disease: From Early Biomarkers to Novel Therapeutic Targets
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 702 Diabetic Kidney Disease: Clinical
Author
- Lee, Wen-Teng, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei City, Taiwan
Group or Team Name
- Shin-Kong CKD Team.
Background
Patients with CKD and T2DM are at higher risk of dementia due to vascular dysfunction and chronic inflammation. GLP-1RAs have shown neuroprotective effects, but their impact in advanced CKD remains unclear. This study evaluated the association between GLP-1RA use and dementia risk in CKD stage 3b+ patients, compared to DPP4is.
Methods
A retrospective cohort study was conducted using electronic health records from 67 U.S. healthcare organizations in the TriNetX network. Adults with CKD stage 3b+ and T2DM, newly prescribed GLP-1RAs or DPP4is between 2015–2020, were included. Patients with prior exposure, recent dementia diagnosis, or hospitalization were excluded. Outcomes included incident dementia, Alzheimer’s disease, vascular and frontotemporal dementia, Parkinson’s disease, movement disorders, and dementia with Lewy bodies. Follow-up was 90 days to 5 years. Analyses used Kaplan–Meier curves and Cox models.
Results
GLP-1RA use was associated with lower risk of dementia (HR 0.80, 95% CI 0.71–0.91) and Alzheimer’s disease (HR 0.76, 95% CI 0.59–0.98) compared to DPP4is. Other outcomes showed no significant differences.
Conclusion
GLP-1RAs may reduce dementia and Alzheimer’s disease risk in advanced CKD, supporting potential neuroprotective effects beyond glycemic control.
Neurodegenerative Outcomes Comparison from GLP-1RAs and DPP4is
| Clinical Outcomes | GLP-1RAs (n = 12,351) | DDP4is (n = 12,351) | GLP-1RAs vs. DDP4is |
| Dementia | 455 (3.7) | 562 (4.6) | 0.80 (0.71–0.91) (p=0.001) |
| Alzheimer | 109 (0.9) | 142 (1.1) | 0.76 (0.59–0.98) (p=0.033) |
| Vascular dementia | 173 (1.4) | 182 (1.5) | 0.95 (0.77–1.16) (p=0.591) |
| Frontotemporal dementia | 10 (0.1) | 14 (0.1) | 0.64 (0.28–1.48) (p=0.294) |
| Dementia with Lewy bodies | 11 (0.1) | 15 (0.1) | 0.74 (0.34–1.61) (p=0.443) |
| Parkinson | 178 (1.4) | 177 (1.4) | 1.00 (0.81–1.23) (p=0.992) |
| Extrapyramidal and movement disorders | 1,057 (8.6) | 994 (8.0) | 1.06 (0.97–1.16) (p=0.178) |
Funding
- Government Support – Non-U.S.