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Association between glucagon-like peptide-1 receptor agonists and risk of dementia in older adults with type 2 diabetes: A target trial emulation
Zhou T, Tang H, Zhang B, Zhang D, Lu Y, Li L, Chen J, Chen Y et al.. Diabetes, obesity & metabolism, 2025-12-22
Topic: Risk, prevention and care in population studies
Aim Type 2 diabetes (T2D) is associated with increased dementia risk, but comparative data across newer glucose-lowering therapies remain limited. We examined whether the initiation of GLP-1 receptor agonists (GLP-1 RAs) was associated with incident dementia compared with DPP4 inhibitors (DPP4is) and SGLT2 inhibitors (SGLT2is) in older adults with T2D. Materials and methods We conducted a retrospective cohort study emulating a target trial using electronic health records from the University of Pennsylvania Health System (2019-2024), with external validation in the TriNetX U.S. Collaborative Network. Adults aged ≥50 with T2D, no prior dementia, and no GLP-1 RA, DPP4i, or SGLT2i use in the previous year were eligible. New GLP-1 RA users were propensity-score matched (1:1) to DPP4i users (n = 6677 pairs) and SGLT2i users (n = 8434 pairs). The outcome was incident dementia, defined by ICD-10-CM codes. Cox proportional hazards models estimated hazard ratios (HRs), with multiple sensitivity and subgroup analyses performed. Results Over a median follow-up of 3.0 years (GLP-1 RA vs. DPP4i) and 2.4 years (GLP-1 RA vs. SGLT2i), GLP-1 RA use was associated with a lower dementia risk versus DPP4is (109 vs. 148 events; HR 0.76, 95% CI 0.59-0.97), but a higher risk versus SGLT2is (127 vs. 64 events; HR 1.53, 95% CI 1.13-2.07). Findings were consistent across sensitivity and subgroup analyses. External validation confirmed reduced dementia risk versus DPP4is but not versus SGLT2is. Conclusions In this large real-world cohort, GLP-1 RAs were associated with lower dementia risk than DPP4is but higher risk than SGLT2is. Prospective, biomarker-informed studies are needed to clarify mechanisms and inform treatment choices in older adults with T2D.
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APA 7th
Zhou, T., Tang, H., Zhang, B., Zhang, D., Lu, Y., Li, L., et al. (2026). Association between glucagon-like peptide-1 receptor agonists and risk of dementia in older adults with type 2 diabetes: A target trial emulation. Diabetes, obesity & metabolism. https://doi.org/10.1111/dom.70384
Vancouver
Zhou T, Tang H, Zhang B, Zhang D, Lu Y, Li L, et al. Association between glucagon-like peptide-1 receptor agonists and risk of dementia in older adults with type 2 diabetes: A target trial emulation. Diabetes, obesity & metabolism. 2026. doi:10.1111/dom.70384. PMID: 41424236.
BibTeX
@article{zhou2026-41424236,
author = {Zhou, T. and Tang, H. and Zhang, B. and Zhang, D. and Lu, Y. and Li, L. and Chen, J. and Chen, Y. and others},
title = {{Association between glucagon-like peptide-1 receptor agonists and risk of dementia in older adults with type 2 diabetes: A target trial emulation}},
journal = {Diabetes, obesity \& metabolism},
year = {2026},
doi = {10.1111/dom.70384},
pmid = {41424236},
url = {https://doi.org/10.1111/dom.70384}
}
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Key findings
- Aim Type 2 diabetes (T2D) is associated with increased dementia risk, but comparative data across newer glucose-lowering therapies remain limited.
- We examined whether the initiation of GLP-1 receptor agonists (GLP-1 RAs) was associated with incident dementia compared with DPP4 inhibitors (DPP4is) and SGLT2 inhibitors (SGLT2is) in older adults with T2D.
- Results Over a median follow-up of 3.0 years (GLP-1 RA vs.
- SGLT2i), GLP-1 RA use was associated with a lower dementia risk versus DPP4is (109 vs. 148 events; HR 0.76, 95% CI 0.59-0.97), but a higher risk versus SGLT2is (127 vs. 64 events; HR 1.53, 95% CI 1.13-2.07).
- External validation confirmed reduced dementia risk versus DPP4is but not versus SGLT2is.
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Study details
- Study designcohort study
- Participants6,677
- Effect sizeHR 0.76; HR 1.53
- 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 (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 | 3 / 4 | 6,677 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 41424236) |
| 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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