Neurodegeneration onset with glucagon-like peptide-1 receptor agonists in people with type 2 diabetes: a real-world multinational cohort study
Authors' conclusion
In a real-world cohort of people living with T2D with a multinational representation, the initiation of GLP-1 RAs, compared to DPP4i or basal insulin, was associated with a lower risk of new-onset neurodegeneration. These data support the rationale for dedicated clinical trials to assess the potential neuroprotective properties of GLP-1 RAs in this population.
Study context
- Population
- People with T2D lacking evidence of neurodegeneration initiating GLP-1 RAs or DPP4i (2010–2021); TriNetX platform; 109,731 women, mean age 58.6 years (SD 12), mean HbA1c 7.7% (1.4)matched
- Participants
- 214,442 people
- Exposure
- GLP-1 RA initiation vs DPP4i initiation
- Outcome
- Composite of:
- New neurodegenerative conditions
- Incl. Alzheimer's disease
- Parkinson's disease
- Dementia subtypes
- Other synucleinopathies
- Follow-up
- ≤ 5 years
Methodological detailspropensity-score matched (1:1), multinational, real-world, TriNetX electronic health records
- Propensity-score matched (1:1)
- Multinational
- Real-world
- TriNetX electronic health records
Main finding
As reported in the abstract
Neurodegenerative disorder onset · 4.0-year mean follow-up
Each group vs DPP4iHazard ratio (95% CI)
GLP-1 RAs
0.81(0.77–0.86)
- GLP-1 RAs
- absolute risk difference - 0.6% (95% CI - 0.8 to - 0.5)
Observational data: associations, not effects.
Further findings
Neurodegeneration onset by subgroup (GLP-1 RAs vs DPP4i)
- Women, HR
- 0.78 [0.72 to 0.84]
- Men, HR
- 0.90 [0.83 to 0.98]
- Aged ≥ 65 years, HR
- 0.82 [0.78 to 0.87]
- Aged < 65 years, HR
- 0.84 [0.70 to 1.00]
- Semaglutide, HR
- 0.75 [0.67 to 0.84]
- Liraglutide, HR
- 0.77 [0.70 to 0.84]
- Dulaglutide, HR
- 0.82 [0.77 to 0.88]
Individual components (GLP-1 RAs vs DPP4i)
- Dementia, HR
- 0.76 [0.72 to 0.81]
- Alzheimer's disease, HR
- 0.77 [0.68 to 0.87]
- Vascular dementia, HR
- 0.75 [0.67 to 0.85]
- Parkinson's disease, HR
- 1.04 [0.93 to 1.17]
GLP-1 RAs vs basal insulin (separate cohort)
- Results in the same direction as vs DPP4i
Original publication
Neurodegeneration onset with glucagon-like peptide-1 receptor agonists in people with type 2 diabetes: a real-world multinational cohort study. Cardiovasc Diabetol. Published 7 November 2025. doi:10.
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