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Effects of GLP-1 receptor agonists on vascular dementia: a systematic review and meta-analysis
Stefanou MI, Tentolouris A, Panagiotopoulos E, Theodorou A, Mengel A, Athanasaki A, Lambadiari V, Peppa M et al.. Journal of diabetes and its complications, 2026-01-26
Topic: Brain proteins, microglia and lab models
Background and aims Vascular dementia (VaD) is strongly associated with type 2 diabetes (T2DM), overweight, and obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce cardiovascular risk and exhibit neuroprotective properties, yet their effects in incident VaD remain uncertain. This study evaluated whether GLP-1 RAs have preventive potential for VaD in adults with T2DM, overweight, or obesity. Methods A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was conducted to estimate the risk of incident VaD among patients with T2DM or overweight/obesity treated with GLP-1 RAs versus placebo. Data were pooled using a random-effects model, with outcomes expressed as risk ratios (RRs) and 95% confidence intervals (CIs). Subgroup analysis was performed after stratification by population type (T2DM vs. overweight/obesity), and meta-regression assessed the association between RCT duration and effect size. Results Seven RCTs (six in T2DM, one in overweight/obesity) comprising 61,610 participants were included. GLP-1 RA treatment was not associated with a statistically significant difference in VaD incidence (RR: 0.50; 95% CI: 0.19-1.32; I 2 = 0%). Subgroup analysis revealed no significant between-group differences (p for subgroups = 0.612), although numerically lower VaD rates were observed in the T2DM subgroup (RR: 0.38; 95% CI: 0.13-1.11). Meta-regression did not demonstrate a significant association between follow-up duration and treatment effect (β = -0.291; SE = 0.212; 95% CI: -0.843 to 0.262; p = 0.229). Conclusions The pooled evidence did not confirm a statistically significant reduction in VaD risk with GLP-1 RA therapy. Numerically lower VaD incidence in T2DM populations warrants further investigation in adequately powered and systematically adjudicated trials.
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APA 7th
Stefanou, M. I., Tentolouris, A., Panagiotopoulos, E., Theodorou, A., Mengel, A., Athanasaki, A., et al. (2026). Effects of GLP-1 receptor agonists on vascular dementia: a systematic review and meta-analysis. Journal of diabetes and its complications. https://doi.org/10.1016/j.jdiacomp.2026.109271
Vancouver
Stefanou MI, Tentolouris A, Panagiotopoulos E, Theodorou A, Mengel A, Athanasaki A, et al. Effects of GLP-1 receptor agonists on vascular dementia: a systematic review and meta-analysis. Journal of diabetes and its complications. 2026. doi:10.1016/j.jdiacomp.2026.109271. PMID: 41619622.
BibTeX
@article{stefanou2026-41619622,
author = {Stefanou, M. I. and Tentolouris, A. and Panagiotopoulos, E. and Theodorou, A. and Mengel, A. and Athanasaki, A. and Lambadiari, V. and Peppa, M. and others},
title = {{Effects of GLP-1 receptor agonists on vascular dementia: a systematic review and meta-analysis}},
journal = {Journal of diabetes and its complications},
year = {2026},
doi = {10.1016/j.jdiacomp.2026.109271},
pmid = {41619622},
url = {https://doi.org/10.1016/j.jdiacomp.2026.109271}
}
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Key findings
- Background and aims Vascular dementia (VaD) is strongly associated with type 2 diabetes (T2DM), overweight, and obesity.
- Methods A systematic review and meta-analysis of randomized-controlled clinical trials (RCTs) was conducted to estimate the risk of incident VaD among patients with T2DM or overweight/obesity treated with GLP-1 RAs versus placebo.
- Results Seven RCTs (six in T2DM, one in overweight/obesity) comprising 61,610 participants were included.
- GLP-1 RA treatment was not associated with a statistically significant difference in VaD incidence (RR: 0.50; 95% CI: 0.19-1.32; I 2 = 0%).
- Subgroup analysis revealed no significant between-group differences (p for subgroups = 0.612), although numerically lower VaD rates were observed in the T2DM subgroup (RR: 0.38; 95% CI: 0.13-1.11).
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Study details
- Study designsystematic review
- Participants61,610
- Effect sizeRR: 0.50; RR: 0.38
- Evidence strengthHigh
How this study scored 88/100
Published in a peer-reviewed journal, and it is a systematic review of all the studies on the question. 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 51 of the 58 points we could judge it on, which is 88 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of diabetes and its complications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 12 / 12 | A systematic review of all the studies on the question |
| 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 4 / 4 | 61,610 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 | A review of other studies — randomization is not credited here |
| 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 41619622) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 51 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 51 of the 58 points we could judge it on is 88 out of 100. |
| Total | 88 / 100 | — |
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