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Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for incident dementia: A retrospective multicohort study
Anagnostakis F, Kokkorakis M, Nagarajan S, Anastasiou G, Mantzoros CS.. Diabetes, obesity & metabolism, 2025-11-27
Topic: Risk, prevention and care in population studies
Objective This study provides real-world evidence on the comparative effectiveness of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) regarding the risk of incident dementia in adults with type 2 diabetes mellitus (T2DM). Research design and methods This cohort study utilised electronic health records from TriNetX (1 April 2013 to 31 December 2019). Adults with T2DM on metformin who initiated GLP-1 RAs or SGLT2i were analysed using Cox proportional hazards models in 1:1 propensity score-matched cohorts. The primary outcome was all-cause dementia; secondary outcomes included vascular and Alzheimer's dementia. Confounding variables were adjusted. Results Among 16 271 participants using GLP-1 RAs and 16 271 using SGLT2i over a median 6.3-year follow-up, 581 GLP-1 RA users and 572 SGLT2i users developed dementia. No significant differences were observed in all-cause dementia (hazard ratio: 1.01, 95% confidence interval: 0.90-1.13), vascular, or Alzheimer's dementia. Subgroup analyses confirmed these findings. Conclusions SGLT2i use was not associated with increased risk of dementia compared with GLP-1RAs in patients with T2DM. Further research is warranted to explore the effects of (newer) incretin-based (co-)agonists on cognitive outcomes.
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APA 7th
Anagnostakis, F., Kokkorakis, M., Nagarajan, S., Anastasiou, G., & Mantzoros, C. S. (2026). Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for incident dementia: A retrospective multicohort study. Diabetes, obesity & metabolism. https://doi.org/10.1111/dom.70336
Vancouver
Anagnostakis F, Kokkorakis M, Nagarajan S, Anastasiou G, Mantzoros CS. Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for incident dementia: A retrospective multicohort study. Diabetes, obesity & metabolism. 2026. doi:10.1111/dom.70336. PMID: 41309383.
BibTeX
@article{anagnostakis2026-41309383,
author = {Anagnostakis, F. and Kokkorakis, M. and Nagarajan, S. and Anastasiou, G. and Mantzoros, C. S.},
title = {{Comparative effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists for incident dementia: A retrospective multicohort study}},
journal = {Diabetes, obesity \& metabolism},
year = {2026},
doi = {10.1111/dom.70336},
pmid = {41309383},
url = {https://doi.org/10.1111/dom.70336}
}
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Key findings
- Results Among 16 271 participants using GLP-1 RAs and 16 271 using SGLT2i over a median 6.3-year follow-up, 581 GLP-1 RA users and 572 SGLT2i users developed dementia.
- No significant differences were observed in all-cause dementia (hazard ratio: 1.01, 95% confidence interval: 0.90-1.13), vascular, or Alzheimer's dementia.
- Subgroup analyses confirmed these findings.
- Conclusions SGLT2i use was not associated with increased risk of dementia compared with GLP-1RAs in patients with T2DM.
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Study details
- Study designcohort study
- Participants271
- Evidence strengthModerate
How this study scored 71/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for effect reported 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 41 of the 58 points we could judge it on, which is 71 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Diabetes, obesity & 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 | 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 | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 2 / 4 | 271 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| 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 41309383) |
| Free to read | 2 / 2 | Free to read |
| Points | 41 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 41 of the 58 points we could judge it on is 71 out of 100. |
| Total | 71 / 100 | — |
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