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Randomized metformin and cognitive outcomes in the Diabetes Prevention Program Outcomes Study
Wander PL, Doherty L, Pan Q, Carmichael O, Turner R, Kuo S, Munshi M, Wallia A et al.. medRxiv, 2026-08-07
Topic: Drug trials: efficacy and safety
Results Total metformin exposure (mean ± SD) was 15.5 ±7.7 years/person in the metformin group. Overall, the frequency distributions of the cognitive syndromes did not differ significantly by treatment group; however, randomization to metformin was associated with a 60% (OR 0.40 [95%CI 0.17, 0.97]) and 62% (OR 0.38 [95%CI 0.16, 0.89]) lower odds of dementia compared with placebo and ILS, respectively, after adjustment for demographics, education, income, and APOE-ε4 genotype. Randomization to metformin was also associated with significantly better memory performance over time (β=0.58; 95%CI: 0.09, 1.1; p=0.02; Cohen’s d=0.1). Conclusions and Relevance Long-term metformin treatment is associated with a reduced risk of dementia and better memory performance among persons with pre-diabetes or T2D. Longer follow-up with more dementia cases is needed to confirm our findings. Findings Randomization to metformin in the Diabetes Prevention Program was associated with a lower risk of dementia in the Diabetes Prevention Program Outcomes Study compared with the randomization to placebo or randomization to intensive lifestyle intervention, but the overall distribution of cognitive impairment syndromes did not differ significantly by treatment group.
Key findings
- Results Total metformin exposure (mean ± SD) was 15.5 ±7.7 years/person in the metformin group.
- Overall, the frequency distributions of the cognitive syndromes did not differ significantly by treatment group; however, randomization to metformin was associated with a 60% (OR 0.40 [95%CI 0.17, 0.97]) and 62% (OR 0.38 [95%CI 0.16, 0.89]) lower odds of dementia compared with placebo and ILS, respectively, after adjustment for demographics, education, income, and APOE-ε4 genotype.
- Randomization to metformin was also associated with significantly better memory performance over time (β=0.58; 95%CI: 0.09, 1.1; p=0.02; Cohen’s d=0.1).
- Conclusions and Relevance Long-term metformin treatment is associated with a reduced risk of dementia and better memory performance among persons with pre-diabetes or T2D.
- Longer follow-up with more dementia cases is needed to confirm our findings.
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Study details
- Study designlongitudinal study
- Participants1,483
- Effect sizeor 3.2; OR 0.40; OR 0.38
- Evidence strengthHigh
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 55 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. We have no data on 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 multi-centre collaboration, so those were left out: it earned 34 of the 62 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| How recent | 5 / 5 | 2026 — within 1 year(s) of the newest study here |
| Sample size | 3 / 4 | 1,483 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) |
| Randomised / blinded | 1 / 2 | Randomised (as stated in the record) |
| 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 | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 34 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 34 of the 62 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | Capped to 16 because this is not a peer-reviewed article. |
What each of these 20 components measures, and what this score is not →
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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's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Wander, P. L., Doherty, L., Pan, Q., Carmichael, O., Turner, R., Kuo, S., et al. (2026). Randomized metformin and cognitive outcomes in the Diabetes Prevention Program Outcomes Study. medRxiv. https://doi.org/10.64898/2026.08.05.26359234
Vancouver
Wander PL, Doherty L, Pan Q, Carmichael O, Turner R, Kuo S, et al. Randomized metformin and cognitive outcomes in the Diabetes Prevention Program Outcomes Study. medRxiv. 2026. doi:10.64898/2026.08.05.26359234.
BibTeX
@article{wander2026-f474ce0b,
author = {Wander, P. L. and Doherty, L. and Pan, Q. and Carmichael, O. and Turner, R. and Kuo, S. and Munshi, M. and Wallia, A. and others},
title = {{Randomized metformin and cognitive outcomes in the Diabetes Prevention Program Outcomes Study}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.08.05.26359234},
url = {https://doi.org/10.64898/2026.08.05.26359234}
}
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