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Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study
Koenig AM, Mechanic-Hamilton D, Xie SX, Combs MF, Cappola AR, Xie L, Detre JA, Wolk DA et al.. Alzheimer disease and associated disorders, 2017-04-01
Topic: Amyloid, tau and blood-test diagnosis
Epidemiological studies have identified a robust association between type II diabetes mellitus and Alzheimer disease (AD), and neurobiological studies have suggested the presence of central nervous system insulin resistance in individuals with AD. Given this association, we hypothesized that the central nervous system-penetrant insulin-sensitizing medication metformin would be beneficial as a disease-modifying and/or symptomatic therapy for AD, and conducted a placebo-controlled crossover study of its effects on cerebrospinal fluid (CSF), neuroimaging, and cognitive biomarkers. Twenty nondiabetic subjects with mild cognitive impairment or mild dementia due to AD were randomized to receive metformin then placebo for 8 weeks each or vice versa. CSF and neuroimaging (Arterial Spin Label MRI) data were collected for biomarker analyses, and cognitive testing was performed. Metformin was found to be safe, well-tolerated, and measureable in CSF at an average steady-state concentration of 95.6 ng/mL. Metformin was associated with improved executive functioning, and trends suggested improvement in learning/memory and attention. No significant changes in cerebral blood flow were observed, though post hoc completer analyses suggested an increase in orbitofrontal cerebral blood flow with metformin exposure. Further study of these findings is warranted.
Key findings
- Metformin was associated with improved executive functioning, and trends suggested improvement in learning/memory and attention.
- No significant changes in cerebral blood flow were observed, though post hoc completer analyses suggested an increase in orbitofrontal cerebral blood flow with metformin exposure.
- Further study of these findings is warranted.
Why it matters
In a small pilot study of 20 people with mild cognitive impairment or mild Alzheimer's dementia, metformin was safe and associated with improved executive functioning, with trends toward improvement in learning, memory, and attention. No significant change in cerebral blood flow was observed, and the authors say further study is needed, so this does not establish metformin as a treatment.
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Study details
- Evidence strengthHigh
How this study scored 69/100
Published in a peer-reviewed journal, and it is a randomised controlled trial. Scored zero for sample size and effect reported because the record does not state it.
| 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 | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| 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 | 2 / 5 | 2017 — within 10 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 | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 6 / 7 | Cited 349 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 31.7 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 4 / 6 | Cited 15.2× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 9 other studies in this library |
| Still being cited | 3 / 4 | Cited 102 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Steven Edward Arnold: h-index 125 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Massachusetts General Hospital: institution h-index 2,057 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 2 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28538088) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 69 / 100 | — |
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Read the original
- DOI: 10.1097/wad.0000000000000202
- PubMed: 28538088
- Original source →
- Free full text: PubMed Central →
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'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
Koenig, A. M., Mechanic-Hamilton, D., Xie, S. X., Combs, M. F., Cappola, A. R., Xie, L., et al. (2017). Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study. Alzheimer disease and associated disorders. https://doi.org/10.1097/wad.0000000000000202
Vancouver
Koenig AM, Mechanic-Hamilton D, Xie SX, Combs MF, Cappola AR, Xie L, et al. Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study. Alzheimer disease and associated disorders. 2017. doi:10.1097/wad.0000000000000202. PMID: 28538088.
BibTeX
@article{koenig2017-28538088,
author = {Koenig, A. M. and Mechanic-Hamilton, D. and Xie, S. X. and Combs, M. F. and Cappola, A. R. and Xie, L. and Detre, J. A. and Wolk, D. A. and others},
title = {{Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study}},
journal = {Alzheimer disease and associated disorders},
year = {2017},
doi = {10.1097/wad.0000000000000202},
pmid = {28538088},
url = {https://doi.org/10.1097/wad.0000000000000202}
}
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