Association between glucagon‐like peptide‐1 receptor agonists and risk of dementia in older adults with type 2 diabetes: A target trial emulation
Authors' conclusion
In this large real-world cohort, GLP-1 RAs were associated with lower dementia risk than DPP4is but higher risk than SGLT2is. Prospective, biomarker-informed studies are needed to clarify mechanisms and inform treatment choices in older adults with T2D.
Study context
- Population
- Adults aged ≥50 with T2D, no prior dementia, and no GLP-1 RA, DPP4i or SGLT2i use in the previous year; University of Pennsylvania Health System (2019–2024)6,677 and 8434 matched pairs
- Exposure
- GLP-1 RA initiation vs DPP4i and vs SGLT2i
- Outcome
- Incident dementia, defined by ICD-10-CM codes
- Follow-up
- Median 3.0 years (GLP-1 RA vs DPP4i) and 2.4 years (GLP-1 RA vs SGLT2i)
Methodological detailspropensity-score matched (1:1), electronic health records, external validation in TriNetX U.S. Collaborative Network
- Propensity-score matched (1:1)
- Electronic health records
- External validation in TriNetX U.S. Collaborative Network
Main finding
As reported in the abstract
Incident dementia
Hazard ratio (95% CI)
GLP-1 RAvs DPP4i109 vs 148 events; median follow-up 3.0 years
0.76(0.59–0.97)
GLP-1 RAvs SGLT2i127 vs 64 events; median follow-up 2.4 years
1.53(1.13–2.07)
Observational data: associations, not effects.
Further findings
Sensitivity and subgroup analyses
- Findings were consistent across sensitivity and subgroup analyses
External validation (TriNetX)
- External validation confirmed reduced dementia risk vs DPP4 inhibitors (DPP4is) but not vs SGLT2 inhibitors (SGLT2is)
Original publication
Association between glucagon‐like peptide‐1 receptor agonists and risk of dementia in older adults with type 2 diabetes: A target trial emulation. Diabetes Obes Metab. Published 22 December 2025. doi:10.
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