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Comparative effectiveness of SGLT2 inhibitors and GLP-1 receptor agonists in preventing Alzheimer's disease, vascular dementia, and other dementia types among patients with type 2 diabetes
Sun M, Wang X, Lu Z, Yang Y, Lv S, Miao M, Chen WM, Wu SY et al.. Diabetes & metabolism, 2025-02-12
Topic: Amyloid, tau and blood-test diagnosis
Background Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). While sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists have shown neuroprotective potential, comparative data on their efficacy in dementia prevention remain scarce. Methods - We conducted a retrospective cohort study using the TriNetX database, including 307,103 SGLT2 inhibitor users and 348,686 GLP-1 receptor agonist users with T2DM. Propensity score matching yielded 221,883 pairs with balanced baseline characteristics. The primary outcome was overall dementia incidence, with secondary outcomes including AD, VaD, and all-cause mortality. Hazard ratios (HRs) were calculated using Cox proportional hazards models. Results SGLT2 inhibitors were associated with a significantly lower incidence of overall dementia compared to GLP-1 receptor agonists (2.7 % vs. 3.6 %; HR, 0.92; 95 % CI, 0.89-0.95). The risk of VaD (HR, 0.89; 95 % CI, 0.84-0.95) and AD (HR, 0.90; 95 % CI, 0.86-0.94) was also reduced with SGLT2 inhibitors. All-cause mortality was lower in the SGLT2 group (3.6 % vs. 4.6 %; HR, 0.95; 95 % CI, 0.92-0.98). No significant difference was observed in other dementia subtypes (HR, 0.96; 95 % CI, 0.91-1.01). Conclusions In this large, real-world cohort, SGLT2 inhibitors demonstrated superior efficacy over GLP-1 receptor agonists in reducing the risks of overall dementia, VaD, and AD among patients with T2DM. These findings support the preferential use of SGLT2 inhibitors in mitigating dementia risk in this population, though randomized controlled trials are warranted for confirmation.
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APA 7th
Sun, M., Wang, X., Lu, Z., Yang, Y., Lv, S., Miao, M., et al. (2025). Comparative effectiveness of SGLT2 inhibitors and GLP-1 receptor agonists in preventing Alzheimer's disease, vascular dementia, and other dementia types among patients with type 2 diabetes. Diabetes & metabolism. https://doi.org/10.1016/j.diabet.2025.101623
Vancouver
Sun M, Wang X, Lu Z, Yang Y, Lv S, Miao M, et al. Comparative effectiveness of SGLT2 inhibitors and GLP-1 receptor agonists in preventing Alzheimer's disease, vascular dementia, and other dementia types among patients with type 2 diabetes. Diabetes & metabolism. 2025. doi:10.1016/j.diabet.2025.101623. PMID: 39952607.
BibTeX
@article{sun2025-39952607,
author = {Sun, M. and Wang, X. and Lu, Z. and Yang, Y. and Lv, S. and Miao, M. and Chen, W. M. and Wu, S. Y. and others},
title = {{Comparative effectiveness of SGLT2 inhibitors and GLP-1 receptor agonists in preventing Alzheimer's disease, vascular dementia, and other dementia types among patients with type 2 diabetes}},
journal = {Diabetes \& metabolism},
year = {2025},
doi = {10.1016/j.diabet.2025.101623},
pmid = {39952607},
url = {https://doi.org/10.1016/j.diabet.2025.101623}
}
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Key findings
- Background Type 2 diabetes mellitus (T2DM) is associated with an elevated risk of dementia, including Alzheimer's disease (AD) and vascular dementia (VaD).
- The primary outcome was overall dementia incidence, with secondary outcomes including AD, VaD, and all-cause mortality.
- Results SGLT2 inhibitors were associated with a significantly lower incidence of overall dementia compared to GLP-1 receptor agonists (2.7 % vs. 3.6 %; HR, 0.92; 95 % CI, 0.89-0.95).
- No significant difference was observed in other dementia subtypes (HR, 0.96; 95 % CI, 0.91-1.01).
- Conclusions In this large, real-world cohort, SGLT2 inhibitors demonstrated superior efficacy over GLP-1 receptor agonists in reducing the risks of overall dementia, VaD, and AD among patients with T2DM.
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Study details
- Study designcohort study
- Evidence strengthHigh
How this study scored 60/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for sample size, effect reported, studied in people and 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 35 of the 58 points we could judge it on, which is 60 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Diabetes & metabolism) |
| 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 | 5 / 5 | Rated “high” 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 | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 39952607) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 35 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 35 of the 58 points we could judge it on is 60 out of 100. |
| Total | 60 / 100 | — |
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