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MCI

CompletedPhase 2Results posted

Metformin in Amnestic Mild Cognitive Impairment

Metformin in the Prevention of Alzheimer's Disease

Lead sponsor

Columbia University

Asset

Metformin

Listed sites

Recruiting sites

Enrollment

actual

Study population

Alzheimer’s disease, MCI / preclinical Alzheimer’s

Key I/E criteria

•Age 55-90•MRI contraindications excluded

Primary endpoints

•Total Recall Score in the Selective Reminding Test•ADAS-Cog

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Other grant270901Alzheimer's Disease Drug Discovery Foundation

Org study IDAAAC7231

NCT IDNCT00620191

NihR01AG026413

Timeline

Milestones

Study first posted2008-02-21estimated

Study start2008-06-01actual

Primary completion2012-02actual (month precision)

Study completion2012-02actual (month precision)

Last update posted2020-10-23actual

Results first posted2020-10-23actual

Assets

Drug assets

Metformin

Study populations

Who this study enrolls

Alzheimer’s diseaseMCI / preclinical Alzheimer’s

Eligibility

Who can enroll

Minimum age55 Years

Maximum age90 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Age range: 55 years to 90 years. The main rationale for this inclusion criteria is to follow the standard set by the Alzheimer's Disease Cooperative Study (ADCS).

•Memory complaint expressed by the participant and recognized by the informant. The memory complaint must represent a change from previous functioning based on information provided by both subject and informant.

•Fluent in English or Spanish.

•Mini-Mental State Examination (MMSE) equal or more than 20.

•Subjects must fulfill criteria for amnestic mild cognitive impairment (MCI). Guidelines for the diagnosis of MCI: Subjects must score below a predetermined cut-off score on the logical memory II delayed paragraph recall sub-test of the Wechsler Memory Scale Revised (WMS-R) or the selective reminding test (SRT).

•Global Clinical Dementia Rating (CDR) score must be 0.5 at screening.

•Subjects without a known history of diabetes or diabetes that has never been treated with medications. If diabetes is diagnosed during screening or they have a history of diabetes not treated in the last 12 months they will be excluded if their Hemoglobin A1c (HbA1c) is > 6.5. In addition, a diagnosis of diabetes can be made if the HbA1c is 6.5% or more.

•Overweight or obese by National Heart, Lung, and Blood Institute (NHLBI) criteria (Body Mass Index (BMI) of more or equal of 25 kg/ m2).

•No contraindications to metformin treatment.

•Hachinski score less or equal to 4.

•Hamilton score less or equal to 12 on the 17 item scale.

•General cognition and functional performance such that a diagnosis of dementia cannot be made at the time of screening based on DSM-IV criteria.

•Vision and hearing must be sufficient for compliance with testing procedures

Exclusion criteria

•Individuals with dementia

•MMSE < 20

•Subjects with neurologic diseases associated to neurologic deficits.

•Subjects with current psychiatric diagnoses such as depression, bipolar disorder or schizophrenia.

•Subjects with uncontrolled hypertension (systolic blood pressure more than 160 mmHg or diastolic blood pressure more than 95 mmHg.

•Subjects with a history of active cancer or cancer within last five years, with the exception of squamous or basal cell carcinoma of the skin.

•Subjects who for any reason may not complete the study as judged by the study physician.

•Subjects with a known history of diabetes treated with medications.

•Subjects with a new or old diagnosis of diabetes, never treated, with a HbA1c of more than 6.5 .

•Contraindications to metformin: Contraindications to metformin use include a creatinine of > 1.5, liver disease by history or by elevated transaminases, congestive heart failure, and alcohol abuse.

•Use of cholinesterase inhibitors.

Exclusion criteria for brain imaging study:

•Presence of diabetes, even if the HbA1c is less or equal to 6.5.

•Inability to lie down for any reason.

•Presence of any metallic implant.

•Claustrophobia.

•Any contraindication to magnetic resonance imaging (MRI) or fluorodeoxyglucose (FDG) positron emission tomography (PET).

Endpoints (8)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Amyloid biomarkers

Global cognition

6 endpoints

Primary/protocol endpoint

Change in Total Recall Score in the Selective Reminding Test

Time frame:12 months

change from baseline, improvement

Primary/protocol endpoint

Change in Score of the Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog)

Time frame:12 months

ADAS-Cog

change from baseline, improvement

Primary/registry result

Change in Total Recall Score in the Selective Reminding Test

Time frame:12 months

change from baseline, improvement

Posted result

Group	Value (mean), score on a scale	Standard deviation
Placebon=40 Participants	5.7	8.7
Metforminn=40 Participants	9.4	8.5

Mean Difference (Net)3.7p0.05t-test, 2 sided

Mean Difference (Net)4.1p0.05ANCOVA

Primary/registry result

Change in Score of the Alzheimer's Disease Assessment Scale-cognitive Subscale (ADAS-cog)

Time frame:12 months

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), score	Standard deviation
Placebon=40 Participants	-1.98	5.5
Metforminn=40 Participants	0.0	3.3

Mean Difference (Final Values)1.98p0.06t-test, 2 sided

Mean Difference (Final Values)0.9p0.34ANCOVA

Secondary/protocol endpoint

Change in Relative Glucose Uptake (rCMRg) in the Posterior Cingulate-precuneus.

Time frame:12 months

ADAS-Cog

change from baseline, improvement

Secondary/registry result

Change in Relative Glucose Uptake (rCMRg) in the Posterior Cingulate-precuneus.

Time frame:12 months

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), percentage of rCMRgl	Standard deviation
Placebon=18 Participants	0.0	6.0
Metforminn=15 Participants	2.0	6.3

Mean Difference (Final Values)2.0p0.36t-test, 2 sided

Amyloid biomarkers

2 endpoints

Other/protocol endpoint

Change in Plasma Amyloid Beta-42

Time frame:12 months

change from baseline, improvement

Other_pre_specified/registry result

Change in Plasma Amyloid Beta-42

Time frame:12 months

change from baseline, improvement

Posted result

Group	Value (mean), pg/ml	Standard deviation
Placebon=40 Participants	-4.40	23.51
Metforminn=40 Participants	0.69	18.5

Mean Difference (Net)5.09p0.34t-test, 2 sided

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Luchsinger JA, Perez T, Chang H, Mehta P, Steffener J, Pradabhan G, Ichise M, Manly J, Devanand DP, Bagiella E. Metformin in Amnestic Mild Cognitive Impairment: Results of a Pilot Randomized Placebo Controlled Clinical Trial. J Alzheimers Dis. 2016;51(2):501-14. doi: 10.3233/JAD-150493.
PMID26890736via RESULT

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.