# Metformin in Alzheimer's dementia Prevention (MAP)

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2021 · $9,597,463

## Abstract

The goal of this proposal, entitled “Metformin in Alzheimer’s dementia Prevention (MAP)”, is to conduct a phase
II/III randomized controlled trial of metformin vs. placebo in the prevention of cognitive decline among persons
at risk for Alzheimer’s dementia, in response to PAR-18-028 “Phase III Clinical Trials for the Spectrum of
Alzheimer’s Disease and Age-related Cognitive Decline”. This MAP proposal is based on the results of a single
site 12-month early Phase II placebo controlled 1:1 randomized trial of short acting metformin 1000 mg twice a
day among 80 persons with late amnestic mild cognitive impairment (aMCI), without diabetes, who were
overweight or obese (clinicaltrials.gov ID NCT00620191; R01AG026413; ADDF 27091), conducted with the goal
of obtaining preliminary data on safety, feasibility, and efficacy. This pilot study showed that the improvement in
one of the primary outcomes, changes in total recall in the selective reminding test was significantly greater in
the metformin arm compared with the placebo arm (9.7 ± 8.5 vs. 5.3 ± 8.5 words; p = 0.02), and this benefit was
highest in those taking the highest dose of metformin. We propose MAP as a follow-up multisite phase II/III 1:1
randomized placebo-controlled trial to test the efficacy of metformin in the prevention of the cognitive decline
associated with Alzheimer’s dementia. MAP will have the following innovations compared with the previous pilot
study: (a) use of the better tolerated long acting form of metformin (Glucophage XR©), with a maximum dose of
2,000 mg a day; b) exclusion of participants who cannot tolerate at least 1000 mg a day of metformin; (c) repeated
cognitive testing during the metformin titration period to account for practice effects; (d) Extension of the definition
of aMCI to include early aMCI; (e) Extension of the trial duration from 12 months to 24 months and the cognitive
testing interval from 3 months to 6 months; (f) use of the Total Recall Score of the Free and Cued Selective
Reminding Test (FC-SRT) as a primary cognitive outcome and the Preclinical Alzheimer Cognitive Composite
from the Alzheimer’s Disease Cooperative Study (ADCS-PACC) as a secondary cognitive outcome; (g) include
hippocampal volume as a biomarker of neurodegeneration, and white matter hyperintensities (WMH) as a marker
of cerebrovascular disease ascertained on brain magnetic resonance imaging (MRI) as secondary subclinical
outcomes in half of the sample; (h) a proposed initial sample size of 370 (185 per arm), extending to a larger
phase III trial based on a priori defined rules. Our primary aim is to compare changes from baseline to 24 months
in verbal memory performance, measured with the Total Recall Score of the FC-SRT, between the metformin
and placebo arms, following an ITT approach. We will examine global cognitive performance, measured with the
ADCS-PACC, as a secondary outcome. We will also examine APOE-e4 genotype as a modifier of the efficacy
of metformin. Our secondary a...

## Key facts

- **NIH application ID:** 10160752
- **Project number:** 5R01AG062624-03
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Jose Alejandro Luchsinger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $9,597,463
- **Award type:** 5
- **Project period:** 2019-08-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10160752

## Citation

> US National Institutes of Health, RePORTER application 10160752, Metformin in Alzheimer's dementia Prevention (MAP) (5R01AG062624-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10160752. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*