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Protocol for a Randomized Phase II/III Double-Blind Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Extended-Release Metformin in Amnestic Mild Cognitive Impairment: Metformin in Alzheimer Dementia Prevention (MAP)
Luchsinger JA, Devanand D, Goldberg TE, Cammack S, Hernández-Santiago G, Oishi K, Jagust W, Baker S et al.. Alzheimer disease and associated disorders, 2025-04-01
Topic: Amyloid, tau and blood-test diagnosis
Background Metformin has been suggested as a possible strategy for the prevention of Alzheimer disease (AD) and AD related dementias. An early phase II clinical trial of short acting metformin versus placebo showed preliminary evidence of efficacy and safety in slowing cognitive decline among persons with amnestic mild cognitive impairment (aMCI) without diabetes. Objective To conduct a phase II/III randomized clinical of extended-release metformin versus placebo in participants with aMCI without diabetes. Methods Ratio of 1:1 randomized placebo-controlled trial of extended-release metformin in 326 persons with aMCI without diabetes, aged 55 to 90 years, lasting 18 months, with 4 visits every 6 months including baseline. The primary outcome is changes in total recall in the Free and Cued Selective Reminding Test. Secondary outcomes include (1) changes in global cognitive performance, measured with the Alzheimer Disease Cooperative Study Preclinical Alzheimer Cognitive Composite (ADCS-PACC); (2) changes in neurodegeneration, ascertained as cortical thickness in areas affected by AD on brain MRI; (3) changes in cerebrovascular disease, ascertained as white matter hyperintensities (WMH) volume on brain MRI; (4) changes in whole brain amyloid ß (Aß) SUVR and in incident amyloid positivity; (5) changes in tau SUVR in a composite brain region comprising medial and inferolateral temporal cortex; (6) changes in plasma AD biomarkers. Conclusion Observational studies and pilot trials suggest that metformin may help prevent cognitive decline in neurodegenerative disorders. This clinical trial aims to assess metformin's potential in preventing cognitive decline in at-risk individuals and its impact on biomarkers indicative of disease modification.
Key findings
- An early phase II clinical trial of short acting metformin versus placebo showed preliminary evidence of efficacy and safety in slowing cognitive decline among persons with amnestic mild cognitive impairment (aMCI) without diabetes.
- Objective To conduct a phase II/III randomized clinical of extended-release metformin versus placebo in participants with aMCI without diabetes.
- Conclusion Observational studies and pilot trials suggest that metformin may help prevent cognitive decline in neurodegenerative disorders.
Why it matters
This is a protocol for a phase II/III trial testing extended-release metformin against placebo in 326 people with amnestic mild cognitive impairment without diabetes. It notes that an earlier small trial of short-acting metformin showed preliminary evidence of safety and efficacy, but the current trial's results are not yet available.
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Study details
- Participants326
- Evidence strengthHigh
How this study scored 54/100
Published in a peer-reviewed journal. Scored zero for study design and effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 52 of the 96 points we could judge it on, which is 54 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Alzheimer disease and associated disorders) |
| Journal's citation record | 1 / 4 | Alzheimer Disease & Associated Disorders: journal h-index 131 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| 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 | 326 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 3 / 7 | Cited 16 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 4 / 6 | Cited 10.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 1 other studies in this library |
| Still being cited | 2 / 4 | Cited 16 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40434891) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 52 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 52 of the 96 points we could judge it on is 54 out of 100. |
| Total | 54 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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
Luchsinger, J. A., Devanand, D., Goldberg, T. E., Cammack, S., Hernández-Santiago, G., Oishi, K., et al. (2025). Protocol for a Randomized Phase II/III Double-Blind Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Extended-Release Metformin in Amnestic Mild Cognitive Impairment: Metformin in Alzheimer Dementia Prevention (MAP). Alzheimer disease and associated disorders. https://doi.org/10.1097/wad.0000000000000677
Vancouver
Luchsinger JA, Devanand D, Goldberg TE, Cammack S, Hernández-Santiago G, Oishi K, et al. Protocol for a Randomized Phase II/III Double-Blind Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Extended-Release Metformin in Amnestic Mild Cognitive Impairment: Metformin in Alzheimer Dementia Prevention (MAP). Alzheimer disease and associated disorders. 2025. doi:10.1097/wad.0000000000000677. PMID: 40434891.
BibTeX
@article{luchsinger2025-40434891,
author = {Luchsinger, J. A. and Devanand, D. and Goldberg, T. E. and Cammack, S. and Hernández-Santiago, G. and Oishi, K. and Jagust, W. and Baker, S. and others},
title = {{Protocol for a Randomized Phase II/III Double-Blind Placebo-Controlled Trial to Evaluate the Safety and Efficacy of Extended-Release Metformin in Amnestic Mild Cognitive Impairment: Metformin in Alzheimer Dementia Prevention (MAP)}},
journal = {Alzheimer disease and associated disorders},
year = {2025},
doi = {10.1097/wad.0000000000000677},
pmid = {40434891},
url = {https://doi.org/10.1097/wad.0000000000000677}
}
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