# Metformin Effect on Brain Function in Insulin Resistant Elderly People

> **NIH NIH R21** · MAYO CLINIC ROCHESTER · 2021 · $49,973

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer's disease (AD) and other forms of dementia are rapidly increasing with the aging of the population,
and show a clear preponderance among people with insulin resistance. Metformin, an insulin sensitizer, is
being examined in clinical trials as an anti-aging drug. However, very little objective data is available regarding
metformin's effect on the brain, a major organ affected by aging. Insulin receptors are widely distributed in the
brain and their disruption causes neuronal dysfunction and AD like changes. Pre-clinical studies suggest that
metformin ameliorates many AD-related changes and stimulate mitochondrial biogenesis. However,
observational human studies among type 2 diabetics (T2D) show either conflicting or equivocal results which
could be related to other co-morbidities. Metformin is a drug with a long track-record showing an excellent
safety profile among elderly people with insulin resistance. We therefore submit the current
exploratory/developmental research proposal to investigate whether metformin enhances brain mitochondrial
function (ATP production) by nuclear Magnetic Spectroscopy (NMRS) and blood flow and the functional
network by functional MRI (fMRI) of different regions of brain, especially those rich in insulin receptors. As a
secondary measurement, we will measure structural changes in the white and grey matter areas of the brain
by MRI. Cognitive function will be assessed by utilizing the computerized NIH Toolbox. This 40 week placebo
controlled double-blind human study will randomize 40 elderly people >65 years with abdominal adiposity and
impaired fasting glucose to either metformin or placebo intervention.
This project represents a new direction for the PI and is a collaborative effort with colleagues at the Mayo Clinic
with expertise in MRI, NMRS, and AD. The study results may lead to a breakthrough in providing either
definitive data or sufficiently strong preliminary data regarding metformin's effect on elderly people with
insulin resistance, on whether the drug enhances their brain mitochondrial function in conjunction
with improvement of brain functional network and cognitive functions. The proposed research is the
essential step needed to pursue a larger grant application involving the use of metformin as an adjutant to
other established life style changes with beneficial effects on the brain.

## Key facts

- **NIH application ID:** 10286096
- **Project number:** 3R21AG060139-02S1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** K Sreekumaran Nair
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $49,973
- **Award type:** 3
- **Project period:** 2018-09-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10286096

## Citation

> US National Institutes of Health, RePORTER application 10286096, Metformin Effect on Brain Function in Insulin Resistant Elderly People (3R21AG060139-02S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10286096. Licensed CC0.

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