Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity
Authors' conclusion
In this cohort study, the use of GLP-1RAs semaglutide and tirzepatide was associated with a lower risk of dementia, stroke, and all-cause mortality in adults with type 2 diabetes and obesity. These findings suggest potential neuroprotective and cerebrovascular benefits of GLP-1RAs beyond glycemic control, warranting further trials to confirm these outcomes.
Study context
- Population
- Adults aged ≥40 years with T2D and obesity initiating semaglutide, tirzepatide or other antidiabetic drugs, without prior neurodegenerative or cerebrovascular disease; TriNetX US network, December 1, 2017, to June 30, 2024after propensity score matching
- Participants
- 60,860 adults
- Exposure
- GLP-1RA vs other antidiabetic drugs
- GLP-1RAn = 30,430
- Other antidiabetic drugn = 30,430reference
- Outcome
- Incidence of neurodegenerative diseases (dementia, Parkinson disease, mild cognitive impairment) and cerebrovascular diseases (stroke, intracerebral hemorrhage)
Methodological detailspropensity score matched, electronic health record-based
- Propensity score matched
- Electronic health record-based
Main finding
As reported in the abstract
Dementia, stroke, Parkinson disease, intracerebral hemorrhage · 7-year follow-up
GLP-1RA vs Other antidiabetic drugHazard ratio (95% CI)
Dementia
0.63(0.50–0.81)
Stroke
0.81(0.70–0.93)
Observational data: associations, not effects.
Secondary outcomes
| Outcome | HR (95% CI) | |
|---|---|---|
| All-cause mortality · 7-year follow-up | 0.70 (0.63–0.78) | |
| 0.512Hazard ratio (log scale) |
Subgroups
- Greater benefits in patients aged ≥60 years, women, and patients with BMI 30 to 40
Original publication
Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity. JAMA Netw Open. Published 1 July 2025. doi:10.
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