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GLP-1 Receptor Agonists vs SGLT2 Inhibitors for Alzheimer’s Disease Risk in Type 2 Diabetes: A Systematic Review and Meta-Analysis
Silva LL, Valverde MES, Silva AMP, Braz LDG, da Silva KK, Aguiar EM, Volta VD, de Oliveira C et al.. medRxiv, 2026-07-24
Topic: Drug trials: efficacy and safety
Purpose People with type 2 diabetes mellitus (DM2) have an increased risk of Alzheimer’s Disease (AD). GLP-1 receptor agonists (GLP-1RAs) and SGLT2 inhibitors (SGLT2i) have emerged as potential interventions to prevent AD and dementia and may provide insights into disease mechanisms. Methods PubMed, Embase, and Cochrane were searched for randomized controlled trials (RCTs), cohort, and case-control studies between January 1, 2006, and April 15, 2025, comparing GLP-1RAs and/or SGLT2i in adults with DM2 without cognitive impairment at baseline. A total of 12 studies met the inclusion criteria (1 RCT and 11 cohort studies). The primary outcome was incident AD and dementia, assessed primarily through adjusted hazard ratio (HR). Secondary outcomes were HbA1C levels and their relation to cognitive protection. A regression analysis was performed to assess the variables that could explain the result obtained. Results GLP-1RAs and SGLT2i consistently demonstrated a reduced risk of AD (HR = 0.72; 95% CI, 0.59–0.87) and dementia (HR = 0.84; 95% CI, 0.76–0.92) compared to other glucose-lowering therapies, with moderate/high heterogeneity and moderate certainty. Also, SGLT2i showed a modest benefit over GLP-1RAs in protecting against AD (HR = 1.07; 95% CI, 1.00–1.14; p = 0.0496), and baseline HbA1c was associated with AD risk estimates among SGLT2i users but not among GLP-1RA users. Conclusion These findings reinforce the potential of GLP-1RAs and SGLT2i as therapeutic options to slow cognitive decline in DM2, possibly depending on glycemic control and central modulation.
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APA 7th
Silva, L. L., Valverde, M. E. S., Silva, A. M. P., Braz, L. D. G., da Silva, K. K., Aguiar, E. M., et al. (2026). GLP-1 Receptor Agonists vs SGLT2 Inhibitors for Alzheimer’s Disease Risk in Type 2 Diabetes: A Systematic Review and Meta-Analysis. medRxiv. https://doi.org/10.64898/2026.07.22.26358702
Vancouver
Silva LL, Valverde MES, Silva AMP, Braz LDG, da Silva KK, Aguiar EM, et al. GLP-1 Receptor Agonists vs SGLT2 Inhibitors for Alzheimer’s Disease Risk in Type 2 Diabetes: A Systematic Review and Meta-Analysis. medRxiv. 2026. doi:10.64898/2026.07.22.26358702.
BibTeX
@article{silva2026-e092d390,
author = {Silva, L. L. and Valverde, M. E. S. and Silva, A. M. P. and Braz, L. D. G. and da Silva, K. K. and Aguiar, E. M. and Volta, V. D. and de Oliveira, C. and others},
title = {{GLP-1 Receptor Agonists vs SGLT2 Inhibitors for Alzheimer’s Disease Risk in Type 2 Diabetes: A Systematic Review and Meta-Analysis}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.07.22.26358702},
url = {https://doi.org/10.64898/2026.07.22.26358702}
}
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.
Key findings
- Purpose People with type 2 diabetes mellitus (DM2) have an increased risk of Alzheimer’s Disease (AD).
- A regression analysis was performed to assess the variables that could explain the result obtained.
- Results GLP-1RAs and SGLT2i consistently demonstrated a reduced risk of AD (HR = 0.72; 95% CI, 0.59–0.87) and dementia (HR = 0.84; 95% CI, 0.76–0.92) compared to other glucose-lowering therapies, with moderate/high heterogeneity and moderate certainty.
- Also, SGLT2i showed a modest benefit over GLP-1RAs in protecting against AD (HR = 1.07; 95% CI, 1.00–1.14; p = 0.0496), and baseline HbA1c was associated with AD risk estimates among SGLT2i users but not among GLP-1RA users.
- Conclusion These findings reinforce the potential of GLP-1RAs and SGLT2i as therapeutic options to slow cognitive decline in DM2, possibly depending on glycemic control and central modulation.
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Study details
- Study designcohort study
- Participants12
- Effect sizeHR = 0.72; HR = 0.84; HR = 1.07
- Evidence strengthHigh
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 50 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for randomised / blinded because the record does not state it. We have no data on 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 multi-centre collaboration, so those were left out: it earned 31 of the 62 points we could judge it on, which is 50 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A cohort study following people over time |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 1 / 4 | 12 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 | — / 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 |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 31 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 31 of the 62 points we could judge it on is 50 out of 100. |
| Total | 50 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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