Home › Research › Drug development
Antidiabetic medications and risk of cognitive disorders in type 2 diabetes: A retrospective cohort study
Ahmad Basil Nasir, Yassine Kilani, Mohammad Aldiabat, Omar Abdelghany, Youssef Hafez, Nitin Desai, Mahmoud Y. Madi, Francis G. Wade et al.. PLoS ONE, 2026-08-24
Topic: Risk, prevention and care in population studies
Among 1,528,885 adults with type 2 diabetes (mean age, 58 years; 49.2% women), GLP-1 receptor agonists plus metformin were associated with lower incidence of vascular dementia (HR, 0.46; 95% CI, 0.37-0.57), mild cognitive disorder (HR, 0.79; 95% CI, 0.66-0.95), and Alzheimer disease (HR, 0.46; 95% CI, 0.31-0.70). SGLT-2 inhibitors plus metformin reduced vascular dementia risk (HR, 0.68; 95% CI, 0.54-0.87) but not other outcomes. Insulin monotherapy was associated with higher incidence of vascular dementia (HR, 3.27; 95% CI, 3.03-3.52), mild cognitive disorder (HR, 1.71; 95% CI, 1.56-1.87), and Alzheimer disease (HR, 1.56; 95% CI, 1.32-1.84). CONCLUSIONS AND RELEVANCE: GLP-1 receptor agonists and SGLT-2 inhibitors combined with metformin were associated with reduced risk of cognitive decline. Insulin monotherapy was associated with higher incidence of all three outcomes; however, this association is likely influenced by confounding by indication, unmeasured markers of diabetes severity (including diabetes duration, cardiovascular and renal disease severity, and microvascular and macrovascular complications), and shorter follow-up among insulin users, and should not be interpreted as a direct drug effect. Because standard Cox models do not account for death as a competing event, reported hazard ratios reflect cause-specific hazards and may not directly correspond to cumulative incidence, particularly for the insulin group, in which mortality and censoring were substantially higher. Antidiabetic medication choice may influence long-term cognitive outcomes and should be considered in diabetes management.
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
APA 7th
Nasir, A. B., Kilani, Y., Aldiabat, M., Abdelghany, O., Hafez, Y., Desai, N., et al. (2026). Antidiabetic medications and risk of cognitive disorders in type 2 diabetes: A retrospective cohort study. PLoS ONE. https://doi.org/10.1371/journal.pone.0356138
Vancouver
Nasir AB, Kilani Y, Aldiabat M, Abdelghany O, Hafez Y, Desai N, et al. Antidiabetic medications and risk of cognitive disorders in type 2 diabetes: A retrospective cohort study. PLoS ONE. 2026. doi:10.1371/journal.pone.0356138. PMID: 42636218.
BibTeX
@article{nasir2026-42636218,
author = {Nasir, Ahmad Basil and Kilani, Yassine and Aldiabat, Mohammad and Abdelghany, Omar and Hafez, Youssef and Desai, Nitin and Madi, Mahmoud Y. and Wade, Francis G. and others},
title = {{Antidiabetic medications and risk of cognitive disorders in type 2 diabetes: A retrospective cohort study}},
journal = {PLoS ONE},
year = {2026},
doi = {10.1371/journal.pone.0356138},
pmid = {42636218},
url = {https://doi.org/10.1371/journal.pone.0356138}
}
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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
Key findings
- Among 1,528,885 adults with type 2 diabetes (mean age, 58 years; 49.2% women), GLP-1 receptor agonists plus metformin were associated with lower incidence of vascular dementia (HR, 0.46; 95% CI, 0.37-0.57), mild cognitive disorder (HR, 0.79; 95% CI, 0.66-0.95), and Alzheimer disease (HR, 0.46; 95% CI, 0.31-0.70).
- SGLT-2 inhibitors plus metformin reduced vascular dementia risk (HR, 0.68; 95% CI, 0.54-0.87) but not other outcomes.
- Insulin monotherapy was associated with higher incidence of vascular dementia (HR, 3.27; 95% CI, 3.03-3.52), mild cognitive disorder (HR, 1.71; 95% CI, 1.56-1.87), and Alzheimer disease (HR, 1.56; 95% CI, 1.32-1.84).
- CONCLUSIONS AND RELEVANCE: GLP-1 receptor agonists and SGLT-2 inhibitors combined with metformin were associated with reduced risk of cognitive decline.
- Insulin monotherapy was associated with higher incidence of all three outcomes; however, this association is likely influenced by confounding by indication, unmeasured markers of diabetes severity (including diabetes duration, cardiovascular and renal disease severity, and microvascular and macrovascular complications), and shorter follow-up among insulin users, and should not be interpreted as a direct drug effect.
Why it matters
In this large observational study of people with type 2 diabetes, GLP-1 receptor agonists plus metformin were linked to lower incidence of vascular dementia, mild cognitive disorder and Alzheimer's disease, while SGLT-2 inhibitors plus metformin reduced only vascular dementia risk. The authors caution that the higher incidence seen with insulin monotherapy is likely due to confounding and should not be read as a direct drug effect.
New to this subject? Start with our plain-English guide: Treatments →
Study details
- Study designcohort study
- Participants1,528,885
- Effect size49.2%
- Evidence strengthModerate
How this study scored 55/100
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.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (PLoS ONE) |
| Journal's citation record | 4 / 4 | PLoS ONE: journal h-index 594 (OpenAlex, 2026-10-29) |
| 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 | 4 / 4 | 1,528,885 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) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 0 / 7 | Cited 0 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 0 / 6 | Cited 0.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 0 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Wing‐Kin Syn: h-index 20 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multicenter collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 42636218) |
| Free to read | 2 / 2 | Free to read |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Related
Studies in the library that share something with this one. The line above each title says what.
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here.
Related studies in Drug development
Also tagged “incidence”
1,084 studies in the library carry the topic tag “incidence”; these are this study's neighbours in a fixed, alphabetical-by-hash tour of them, not the closest in content. All 1,084 tagged studies.