Evidence map›Paper›PMID 28538088›Full record

Trial reportAlzheimer disease and associated disorders

Effects of the Insulin Sensitizer Metformin in Alzheimer Disease: Pilot Data From a Randomized Placebo-controlled Crossover Study.

Aaron M Koenig, Dawn Mechanic-Hamilton, Sharon X Xie, Martha F Combs, Anne R Cappola, Long Xie, John A Detre, David A Wolk, Steven E Arnold

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer disease and associated disorders. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05227820 (Anti-Inflammatory, Insulin-Sensitizing Agent for Treatment of Cognitive Decline Due to Degenerative Dementias), which is not on this map. Cited by 194 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
194citing papers in PubMed, 8 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05227820 phase2completednot on this map

Anti-Inflammatory, Insulin-Sensitizing Agent for Treatment of Cognitive Decline Due to Degenerative Dementias

TypeinterventionalSponsorNeurological Associates of West Los AngelesRan2022 to 2022Enrolled23ConditionsAlzheimer DiseaseArmsNE3107
3 · Its place in the literature

Who cites it

194 citing papers in PubMed, 8 syntheses or guidelines pooled it.

  1. Pooled it
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  9. Effects of the SGLT2 inhibitor dapagliflozin in early Alzheimer's disease: A randomized controlled trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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134 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Aaron M Koenig*Penn Memory Center Departments of †Biostatistics and Epidemiology ‡Medicine §Radiology ∥Neurology, University of Pennsylvania, Philadelphia, PA.
Dawn Mechanic-Hamilton
Sharon X Xie
Martha F Combs
Anne R Cappola
Long Xie
John A Detre
David A Wolk
Steven E Arnold

Funding

CORE-- NEUROPATHOLOGYP30AG010124 · UNIVERSITY OF PENNSYLVANIA · 1991 to 2005
$7.2M
NIA NIH HHS P30 AG010124NIBIB NIH HHS P41 EB015893
6 · The paper itself

Abstract

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.

Indexed as

AgedAlzheimer DiseaseCognitive DysfunctionCross-Over StudiesDiabetes Mellitus, Type 2FemaleHumansHypoglycemic AgentsMaleMetforminNeuropsychological TestsHypoglycemic AgentsMetformin

Identifiers

PMID28538088
PMCPMC5476214

What Socratic holds

Texttitle and abstract
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.