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Comparative dementia risk with GLP1 receptor agonists, SGLT2 inhibitors, or DPP4 inhibitors: a population-based cohort study
Wu CY, Alkabbani W, Shah BR, Kapral MK, Edwards JD, Maxwell CJ, et al.. Alzheimer's Research & Therapy, 2025-12-20
Topic: Risk, prevention and care in population studies
In the intention-to-treat analysis, dementia risk was not different between GLP1-RA and DPP4i initiators (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.87–1.04; rates: 6.29 versus 6.64 per 1000 person-years; mean follow-up: 6.54 years); however, continuous GLP1-RA versus DPP4i use was associated with a 21% lower risk (HR 0.79, 95% CI 0.64–0.97; rates: 3.64 versus 4.82; mean follow-up: 2.71 years). SGLT2i versus DPP4i initiation was associated with a 14% lower dementia risk in the intention-to-treat analysis (HR 0.86, 95% CI 0.79–0.94; rates: 4.83 versus 5.60; mean follow-up: 4.91 years), and the as-treated analysis showed greater risk reduction (HR 0.70, 95% CI 0.60–0.82; rates: 3.82 versus 5.46; mean follow-up: 2.43 years). Dementia risk was comparable between GLP1-RA versus SGLT2i in both intention-to-treat (HR 0.98, 95% CI 0.87–1.11; rates: 4.85 versus 4.95; mean follow-up: 5.09 years) and as-treated (HR 1.07, 95% CI 0.85–1.36; rates: 3.71 versus 3.56; mean follow-up: 2.40 years) analyses. In people with type 2 diabetes aged ≥ 60 years, SGLT2i are associated with reduced dementia risk, but dementia risk reduction associated with the GLP1-RAs studied is less certain.
Key findings
- In the intention-to-treat analysis, dementia risk was not different between GLP1-RA and DPP4i initiators (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.87–1.04; rates: 6.29 versus 6.64 per 1000 person-years; mean follow-up: 6.54 years); however, continuous GLP1-RA versus DPP4i use was associated with a 21% lower risk (HR 0.79, 95% CI 0.64–0.97; rates: 3.64 versus 4.82; mean follow-up: 2.71 years).
- SGLT2i versus DPP4i initiation was associated with a 14% lower dementia risk in the intention-to-treat analysis (HR 0.86, 95% CI 0.79–0.94; rates: 4.83 versus 5.60; mean follow-up: 4.91 years), and the as-treated analysis showed greater risk reduction (HR 0.70, 95% CI 0.60–0.82; rates: 3.82 versus 5.46; mean follow-up: 2.43 years).
- Dementia risk was comparable between GLP1-RA versus SGLT2i in both intention-to-treat (HR 0.98, 95% CI 0.87–1.11; rates: 4.85 versus 4.95; mean follow-up: 5.09 years) and as-treated (HR 1.07, 95% CI 0.85–1.36; rates: 3.71 versus 3.56; mean follow-up: 2.40 years) analyses.
- In people with type 2 diabetes aged ≥ 60 years, SGLT2i are associated with reduced dementia risk, but dementia risk reduction associated with the GLP1-RAs studied is less certain.
Why it matters
This population-based cohort study compared dementia risk among people with type 2 diabetes starting different diabetes drugs. SGLT2 inhibitors were associated with reduced dementia risk compared with DPP4 inhibitors, while the dementia risk reduction associated with the GLP1 receptor agonists studied was less certain. It suggests some diabetes drugs may be linked to lower dementia risk, but it does not show a treatment or cure.
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Study details
- Study designcohort
- Participants107,424
- Effect sizeSGLT2i vs DPP4i HR 0.86 (95% CI 0.79-0.94); GLP1-RA vs DPP4i HR 0.95 (0.87-1.04)
- Evidence strengthModerate
Limitations
Observational with propensity weighting; as-treated analyses have short follow-up; older GLP-1 agents dominate the exposure window; UK only.
How this study scored 58/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for randomised / blinded because the record does not state it. We have no data on free to read, so that was left out: it earned 57 of the 98 points we could judge it on, which is 58 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer's Research & Therapy) |
| Journal's citation record | 1 / 4 | Alzheimer s Research & Therapy: journal h-index 146 (OpenAlex, 2026-10-29) |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 4 / 4 | 107,424 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 2 / 7 | Cited 6 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 3.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 6 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Walter Swardfager: h-index 47 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | University of Toronto: institution h-index 1,923 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41420258) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 57 / 98 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 57 of the 98 points we could judge it on is 58 out of 100. |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Wu, C. Y., Alkabbani, W., Shah, B. R., Kapral, M. K., Edwards, J. D., Maxwell, C. J., et al. (2025). Comparative dementia risk with GLP1 receptor agonists, SGLT2 inhibitors, or DPP4 inhibitors: a population-based cohort study. Alzheimer's Research & Therapy. https://doi.org/10.1186/s13195-025-01929-x
Vancouver
Wu CY, Alkabbani W, Shah BR, Kapral MK, Edwards JD, Maxwell CJ, et al. Comparative dementia risk with GLP1 receptor agonists, SGLT2 inhibitors, or DPP4 inhibitors: a population-based cohort study. Alzheimer's Research & Therapy. 2025. doi:10.1186/s13195-025-01929-x. PMID: 41420258.
BibTeX
@article{wu2025-41420258,
author = {Wu, C. Y. and Alkabbani, W. and Shah, B. R. and Kapral, M. K. and Edwards, J. D. and Maxwell, C. J. and others},
title = {{Comparative dementia risk with GLP1 receptor agonists, SGLT2 inhibitors, or DPP4 inhibitors: a population-based cohort study}},
journal = {Alzheimer's Research \& Therapy},
year = {2025},
doi = {10.1186/s13195-025-01929-x},
pmid = {41420258},
url = {https://doi.org/10.1186/s13195-025-01929-x}
}
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