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New-generation antidiabetic medications and dementia risk in older adults with type 2 diabetes: A retrospective cohort study
Cohen A, Levine SZ, Vainstein G, Beeri MS, Weinstein G.. The journal of prevention of Alzheimer's disease, 2025-05-08
Topic: Risk, prevention and care in population studies
Background New-generation antidiabetic medications may have therapeutic potential for dementia, beyond their glycemic effects. However, information from observational studies exploring the association between new-generation antidiabetic use and dementia risk is limited. Objectives To examine the association between new-generation antidiabetic medication use and dementia risk. Design Retrospective cohort study using electronic health records of a large non-profit health maintenance organization. Participants 84,798 dementia-free individuals aged ≥65y with type 2 diabetes. Measurements Antidiabetic medication exposure was based on purchased prescriptions and was used as a time-varying variable. Exposure periods were defined as periods in which either dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose cotransporter-2 inhibitors (SGLT-2i), or glucagon-like peptide-1 analogs (GLP-1a) or their combinations were used, otherwise unexposed. Dementia classification was based on the International Classification of Diseases, Ninth Revision codes or antidementia medication prescriptions. Cox regression models were fitted to quantify the association between antidiabetic medication use and incident dementia. Models were adjusted for 13 potential sources of confounding using inverse-probability weighting. Results Among 84,798 individuals with a mean diabetes onset age of 66.4 ± 7.5 years, the median follow-up for dementia risk was 8.7 years (Q1-Q3: 5.4-12.8). Dementia was diagnosed in 11,642 (13.7%) individuals. New-generation medication use was associated with reduced dementia risk (HR = 0.69; 95% CI, 0.66-0.73) and by drug classes (DPP-4i, HR 0.67 [95% CI 0.63-0.71]; SGLT-2i, 0.63 [95% CI 0.56-0.70], GLP-1a, 0.61 [95% CI 0.54-0.69]. Conclusions The results of this large-scale study suggest that new-generation antidiabetic medication use may be associated with lower dementia risk in older adults with T2D.
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APA 7th
Cohen, A., Levine, S. Z., Vainstein, G., Beeri, M. S., & Weinstein, G. (2025). New-generation antidiabetic medications and dementia risk in older adults with type 2 diabetes: A retrospective cohort study. The journal of prevention of Alzheimer's disease. https://doi.org/10.1016/j.tjpad.2025.100199
Vancouver
Cohen A, Levine SZ, Vainstein G, Beeri MS, Weinstein G. New-generation antidiabetic medications and dementia risk in older adults with type 2 diabetes: A retrospective cohort study. The journal of prevention of Alzheimer's disease. 2025. doi:10.1016/j.tjpad.2025.100199. PMID: 40345929.
BibTeX
@article{cohen2025-40345929,
author = {Cohen, A. and Levine, S. Z. and Vainstein, G. and Beeri, M. S. and Weinstein, G.},
title = {{New-generation antidiabetic medications and dementia risk in older adults with type 2 diabetes: A retrospective cohort study}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2025},
doi = {10.1016/j.tjpad.2025.100199},
pmid = {40345929},
url = {https://doi.org/10.1016/j.tjpad.2025.100199}
}
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Key findings
- Results Among 84,798 individuals with a mean diabetes onset age of 66.4 ± 7.5 years, the median follow-up for dementia risk was 8.7 years (Q1-Q3: 5.4-12.8).
- New-generation medication use was associated with reduced dementia risk (HR = 0.69; 95% CI, 0.66-0.73) and by drug classes (DPP-4i, HR 0.67 [95% CI 0.63-0.71]; SGLT-2i, 0.63 [95% CI 0.56-0.70], GLP-1a, 0.61 [95% CI 0.54-0.69].
- Conclusions The results of this large-scale study suggest that new-generation antidiabetic medication use may be associated with lower dementia risk in older adults with T2D.
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Study details
- Study designcohort study
- Participants84,798
- Effect size13.7%; HR = 0.69; HR 0.67
- Evidence strengthModerate
How this study scored 78/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 45 of the 58 points we could judge it on, which is 78 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (The journal of prevention of Alzheimer's disease) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 84,798 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multicenter collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40345929) |
| Free to read | 2 / 2 | Free to read |
| Points | 45 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 45 of the 58 points we could judge it on is 78 out of 100. |
| Total | 78 / 100 | — |
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