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74/100

✓ Peer-reviewed alzhub usefulness score 74 out of 100. Treatments

Topic: Risk, prevention and care in population studies

Objective To determine whether cardioprotective glucose-lowering therapy (sodium-glucose cotransporter-2 inhibitors [SGLT2is], glucagon-like peptide-1 receptor agonists [GLP-1RAs], metformin, and pioglitazone), compared with controls, was associated with a reduction in risk of dementia or cognitive impairment, and among primary dementia subtypes. Results Twenty-six randomized clinical trials were eligible for inclusion (N = 164 531 participants), of which 23 trials (n = 160 191 participants) reported the incidence of dementia or cognitive impairment, including 12 trials evaluating SGLT2is, 10 trials evaluating GLP-1RAs, and 1 trial evaluating pioglitazone (no trials of metformin were identified). Overall, cardioprotective glucose-lowering therapy was not significantly associated with a reduction in cognitive impairment or dementia (odds ratio [OR], 0.83 [95% CI, 0.60-1.14]). Among drug classes, GLP-1RAs were associated with a statistically significant reduction in dementia (OR, 0.55 [95% CI, 0.35-0.86]), but not SGLT2is (OR, 1.20 [95% CI, 0.67-2.17]; P value for heterogeneity = .04). Conclusions and relevance While cardioprotective glucose-lowering therapies were not associated with an overall reduction in all-cause dementia, this meta-analysis of randomized clinical trials found that glucose lowering with GLP-1RAs was associated with a statistically significant reduction in all-cause dementia.

Key findings

Objective To determine whether cardioprotective glucose-lowering therapy (sodium-glucose cotransporter-2 inhibitors [SGLT2is], glucagon-like peptide-1 receptor agonists [GLP-1RAs], metformin, and pioglitazone), compared with controls, was associated with a reduction in risk of dementia or cognitive impairment, and among primary dementia subtypes.
Results Twenty-six randomized clinical trials were eligible for inclusion (N = 164 531 participants), of which 23 trials (n = 160 191 participants) reported the incidence of dementia or cognitive impairment, including 12 trials evaluating SGLT2is, 10 trials evaluating GLP-1RAs, and 1 trial evaluating pioglitazone (no trials of metformin were identified).
Overall, cardioprotective glucose-lowering therapy was not significantly associated with a reduction in cognitive impairment or dementia (odds ratio [OR], 0.83 [95% CI, 0.60-1.14]).
Among drug classes, GLP-1RAs were associated with a statistically significant reduction in dementia (OR, 0.55 [95% CI, 0.35-0.86]), but not SGLT2is (OR, 1.20 [95% CI, 0.67-2.17]; P value for heterogeneity = .04).
Conclusions and relevance While cardioprotective glucose-lowering therapies were not associated with an overall reduction in all-cause dementia, this meta-analysis of randomized clinical trials found that glucose lowering with GLP-1RAs was associated with a statistically significant reduction in all-cause dementia.

Why it matters

This meta-analysis of 26 randomized clinical trials found that cardioprotective glucose-lowering therapies overall were not significantly associated with reduced risk of dementia or cognitive impairment. However, GLP-1 receptor agonists were associated with a statistically significant reduction in dementia, while SGLT2 inhibitors were not, suggesting a possible drug-class difference that requires further study.

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Study details

Study designmeta-analysis
Participants164
Effect size34.9%
Evidence strengthHigh

How this study scored 74/100

Published in a leading specialty journal, and it is a meta-analysis pooling many studies.

Component	Points	Why
Journal tier	9 / 10	Tier 2 — leading specialty journal (JAMA neurology)
Journal's citation record	2 / 4	JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29)
Study design	12 / 12	A meta-analysis pooling many studies
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	4 / 5	2025 — within 3 year(s) of the newest study here
Sample size	2 / 4	164 participants
Effect reported	2 / 3	Effect reported as a number, without an interval or test
Studied in people	3 / 3	Studied in people (participant count stated)
Randomised / blinded	0 / 2	A review of other studies — randomisation is not credited here
Times cited	4 / 7	Cited 86 times (OpenAlex, 2026-10-10)
Citations per year	4 / 5	28.7 citations a year over 3 year(s) since 2025
Impact for its field and year	6 / 6	Cited 52.1× the average for papers of its field and year (OpenAlex FWCI)
Cited by studies here	2 / 6	Cited by 3 other studies in this library
Still being cited	3 / 4	Cited 86 times in 2024–2026 (2026 still in progress; OpenAlex)
Senior author's track record	1 / 4	Last-listed author Catriona Reddin: h-index 13 (OpenAlex, whole career)
Institution's track record	0 / 3	Ollscoil na Gaillimhe – University of Galway: institution h-index 516 (OpenAlex)
Multi-centre collaboration	1 / 3	OpenAlex lists 2 institution(s) in 1 country
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 40193122)
Free to read	2 / 2	Free to read
Total	74 / 100	—

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Read the original

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

Cite this study APA, Vancouver, BibTeX · download .bib or .ris

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 8 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.

APA 7th

Seminer, A., Mulihano, A., O'Brien, C., Krewer, F., Costello, M., Judge, C., et al. (2025). Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis. JAMA neurology. https://doi.org/10.1001/jamaneurol.2025.0360

Vancouver

Seminer A, Mulihano A, O'Brien C, Krewer F, Costello M, Judge C, et al. Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis. JAMA neurology. 2025. doi:10.1001/jamaneurol.2025.0360. PMID: 40193122.

BibTeX

@article{seminer2025-40193122,
  author  = {Seminer, A. and Mulihano, A. and O'Brien, C. and Krewer, F. and Costello, M. and Judge, C. and O'Donnell, M. and Reddin, C.},
  title   = {{Cardioprotective Glucose-Lowering Agents and Dementia Risk: A Systematic Review and Meta-Analysis}},
  journal = {JAMA neurology},
  year    = {2025},
  doi     = {10.1001/jamaneurol.2025.0360},
  pmid    = {40193122},
  url     = {https://doi.org/10.1001/jamaneurol.2025.0360}
}

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