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GLP-1RA comparative effectiveness against dementia onset relative to other antidiabetic medications in a large, multi-site cohort of patients with type 2 diabetes
Nance N, Gilsanz P, Karter AJ, Finertie H, Schmittdiel JA, An J, Adams AS, Oshiro C et al.. Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025-09-01
Topic: Risk, prevention and care in population studies
Introduction To address gaps in current research, this study aims to compare the impact of exposure to glucagon-like peptide-1 receptor agonists (GLP-1RA) versus sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase 4 inhibitors (DPP4i), and sulfonylureas (SU) on reducing the risk of dementia, using a rigorous targeted learning causal inference approach. Methods Using clinical and claims data from four diverse US health-care systems, we emulated three two-arm trials contrasting sustained treatment with GLP-1RA versus SGLT2i, DPP4i, and SU on dementia diagnosis. We included diabetes patients aged ≥ 60 years who initiated medication between 2014 and 2022. We estimated cumulative risk differences at 2.5 years. Results In Cohort 1, there was no evidence of differential dementia risk between sustained exposure to GLP1-RA versus SGLT2i (adjusted risk difference [aRD] -0.001, 95% confidence interval [CI] -0.004, 0.001). In Cohorts 2 and 3, GLP-1RA was associated with reduced risk of dementia diagnosis compared to DPP4i and SU, respectively (aRD -0.013, 95% CI -0.017, -0.009; aRD -0.016, 95% CI -0.018, -0.015). Discussion Rigorous causal inference analysis suggests that sustained exposure to GLP-1RA may modestly reduce risk of dementia, compared to DPP4i or SU exposure-but not compared to SGLT2i. Highlights We researched the comparative effects of diabetes medications on dementia. We studied a large, diverse observational cohort of patients with diabetes in the United States. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may modestly reduce risk of dementia compared to dipeptidyl peptidase 4 inhibitor or sulfonylurea exposure. GLP-1RAs do not show evidence of dementia risk reduction compared to sodium-glucose cotransporter 2 inhibitors. Physicians may consider this when making prescription decisions with patients.
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APA 7th
Nance, N., Gilsanz, P., Karter, A. J., Finertie, H., Schmittdiel, J. A., An, J., et al. (2025). GLP-1RA comparative effectiveness against dementia onset relative to other antidiabetic medications in a large, multi-site cohort of patients with type 2 diabetes. Alzheimer's & dementia : the journal of the Alzheimer's Association. https://doi.org/10.1002/alz.70621
Vancouver
Nance N, Gilsanz P, Karter AJ, Finertie H, Schmittdiel JA, An J, et al. GLP-1RA comparative effectiveness against dementia onset relative to other antidiabetic medications in a large, multi-site cohort of patients with type 2 diabetes. Alzheimer's & dementia : the journal of the Alzheimer's Association. 2025. doi:10.1002/alz.70621. PMID: 40952016.
BibTeX
@article{nance2025-40952016,
author = {Nance, N. and Gilsanz, P. and Karter, A. J. and Finertie, H. and Schmittdiel, J. A. and An, J. and Adams, A. S. and Oshiro, C. and others},
title = {{GLP-1RA comparative effectiveness against dementia onset relative to other antidiabetic medications in a large, multi-site cohort of patients with type 2 diabetes}},
journal = {Alzheimer's \& dementia : the journal of the Alzheimer's Association},
year = {2025},
doi = {10.1002/alz.70621},
pmid = {40952016},
url = {https://doi.org/10.1002/alz.70621}
}
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Key findings
- Introduction To address gaps in current research, this study aims to compare the impact of exposure to glucagon-like peptide-1 receptor agonists (GLP-1RA) versus sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase 4 inhibitors (DPP4i), and sulfonylureas (SU) on reducing the risk of dementia, using a rigorous targeted learning causal inference approach.
- Methods Using clinical and claims data from four diverse US health-care systems, we emulated three two-arm trials contrasting sustained treatment with GLP-1RA versus SGLT2i, DPP4i, and SU on dementia diagnosis.
- Results In Cohort 1, there was no evidence of differential dementia risk between sustained exposure to GLP1-RA versus SGLT2i (adjusted risk difference [aRD] -0.001, 95% confidence interval [CI] -0.004, 0.001).
- In Cohorts 2 and 3, GLP-1RA was associated with reduced risk of dementia diagnosis compared to DPP4i and SU, respectively (aRD -0.013, 95% CI -0.017, -0.009; aRD -0.016, 95% CI -0.018, -0.015).
- Discussion Rigorous causal inference analysis suggests that sustained exposure to GLP-1RA may modestly reduce risk of dementia, compared to DPP4i or SU exposure-but not compared to SGLT2i.
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Study details
- Evidence strengthModerate
How this study scored 52/100
Published in a leading specialty journal. Scored zero for study design, 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 and institution's track record, so those were left out: it earned 32 of the 61 points we could judge it on, which is 52 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Alzheimer's & dementia : the journal of the Alzheimer's Association) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 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 | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40952016) |
| Free to read | 2 / 2 | Free to read |
| Points | 32 / 61 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 32 of the 61 points we could judge it on is 52 out of 100. |
| Total | 52 / 100 | — |
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