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Neurodegeneration onset with glucagon-like peptide-1 receptor agonists in people with type 2 diabetes: a real-world multinational cohort study
Meir Schechter, Alisa Fishkin, Ofri Mosenzon, Dvora R Sehtman-Shachar, Tali Cukierman-Yaffe, Gil Leibowitz, Genya Aharon-Hananel. Cardiovascular diabetology, 2025-11-07
Topic: Gut, metabolism and diet
Overall, 214,442 matched individuals initiated GLP-1 RAs or DPP4i (109,731 women, mean age 58.6 years [SD 12], and mean HbA1c 7.7% [1.4]). During a 4.0-year mean follow-up, neurodegenerative disorder onset occurred in 2,393 (2.2%) and 3,062 (2.9%) people initiating GLP-1 RAs and DPP4i, respectively (hazard ratio of 0.81 [95% CI 0.77 to 0.86]; absolute risk difference - 0.6% [- 0.8 to - 0.5]). The associations were separately observed among women (0.78 [0.72 to 0.84]) and men (0.90 [0.83 to 0.98]), individuals aged ≥ 65 years old (0.82 [0.78 to 0.87]) or < 65 years old (0.84 [0.70 to 1.00]), and in those initiating semaglutide (0.75 [0.67 to 0.84]), liraglutide (0.77 [0.70 to 0.84]), or dulaglutide (0.82 [0.77 to 0.88]). The hazard ratios for dementia, Alzheimer's disease, vascular dementia, and Parkinson's disease onset were 0.76 [0.72 to 0.81], 0.77 [0.68 to 0.87], 0.75 [0.67 to 0.85], and 1.04 [0.93 to 1.17] with GLP-1 RAs versus DPP4i, respectively. The results were in the same direction when comparing individuals initiating GLP-1 RAs with those initiating basal insulin. In a real-world cohort of people living with T2D with a multinational representation, the initiation of GLP-1 RAs, compared to DPP4i or basal insulin, was associated with a lower risk of new-onset neurodegeneration. These data support the rationale for dedicated clinical trials to assess the potential neuroprotective properties of GLP-1 RAs in this population.
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APA 7th
Schechter, M., Fishkin, A., Mosenzon, O., Sehtman-Shachar, D. R., Cukierman-Yaffe, T., Leibowitz, G., et al. (2025). Neurodegeneration onset with glucagon-like peptide-1 receptor agonists in people with type 2 diabetes: a real-world multinational cohort study. Cardiovascular diabetology. https://doi.org/10.1186/s12933-025-02962-8
Vancouver
Schechter M, Fishkin A, Mosenzon O, Sehtman-Shachar DR, Cukierman-Yaffe T, Leibowitz G, et al. Neurodegeneration onset with glucagon-like peptide-1 receptor agonists in people with type 2 diabetes: a real-world multinational cohort study. Cardiovascular diabetology. 2025. doi:10.1186/s12933-025-02962-8. PMID: 41204243.
BibTeX
@article{schechter2025-41204243,
author = {Schechter, Meir and Fishkin, Alisa and Mosenzon, Ofri and Sehtman-Shachar, Dvora R and Cukierman-Yaffe, Tali and Leibowitz, Gil and Aharon-Hananel, Genya},
title = {{Neurodegeneration onset with glucagon-like peptide-1 receptor agonists in people with type 2 diabetes: a real-world multinational cohort study}},
journal = {Cardiovascular diabetology},
year = {2025},
doi = {10.1186/s12933-025-02962-8},
pmid = {41204243},
url = {https://doi.org/10.1186/s12933-025-02962-8}
}
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 names 7 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
Key findings
- Overall, 214,442 matched individuals initiated GLP-1 RAs or DPP4i (109,731 women, mean age 58.6 years [SD 12], and mean HbA1c 7.7% [1.4]).
- During a 4.0-year mean follow-up, neurodegenerative disorder onset occurred in 2,393 (2.2%) and 3,062 (2.9%) people initiating GLP-1 RAs and DPP4i, respectively (hazard ratio of 0.81 [95% CI 0.77 to 0.86]; absolute risk difference - 0.6% [- 0.8 to - 0.5]).
- The associations were separately observed among women (0.78 [0.72 to 0.84]) and men (0.90 [0.83 to 0.98]), individuals aged ≥ 65 years old (0.82 [0.78 to 0.87]) or < 65 years old (0.84 [0.70 to 1.00]), and in those initiating semaglutide (0.75 [0.67 to 0.84]), liraglutide (0.77 [0.70 to 0.84]), or dulaglutide (0.82 [0.77 to 0.88]).
- The hazard ratios for dementia, Alzheimer's disease, vascular dementia, and Parkinson's disease onset were 0.76 [0.72 to 0.81], 0.77 [0.68 to 0.87], 0.75 [0.67 to 0.85], and 1.04 [0.93 to 1.17] with GLP-1 RAs versus DPP4i, respectively.
- The results were in the same direction when comparing individuals initiating GLP-1 RAs with those initiating basal insulin.
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Study details
- Study designcohort study
- Effect size7.7%; 2.2%; 2.9%
- Evidence strengthModerate
How this study scored 63/100
Published in a peer-reviewed journal, and it is a cohort study following people over time. Scored zero for sample size, studied in people and randomised / 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 free to read, so those were left out: it earned 37 of the 59 points we could judge it on, which is 63 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Cardiovascular diabetology) |
| 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 | 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| 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 | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41204243) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 37 / 59 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 37 of the 59 points we could judge it on is 63 out of 100. |
| Total | 63 / 100 | — |
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