# Metformin for Preventing Frailty in High Risk Older Adults

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $386,951

## Abstract

ABSTRACT
 Frailty is a geriatric syndrome which leads to poor health outcomes in older adults, such as falls, disability,
hospitalization, institutionalization, and death. Due to the dramatic growth in the U.S. aging population and the
health care costs associated with frailty (estimated at more than $18 billion per year), frailty is a major health
care problem. There has been little research into potential pharmacologic interventions that would delay or
reduce the incidence of frailty. Thus, the major goal of this study is to test metformin as a novel intervention for
the prevention of frailty. We propose that diabetes/insulin resistance and inflammation are major contributors to
frailty, and that the use of metformin to modulate diabetes/insulin resistance and inflammation will prevent
and/or ameliorate the progression of frailty.
The rationale for testing metformin for frailty prevention is based on the following:
 1) Insulin resistance has been linked to the pathogenesis of frailty and our own research shows that
 diabetes is a significant predictor of frailty onset or worsening in community-dwelling older adults;
 2) Several studies have shown that frail older subjects (compared with non-frail) are under a state of chronic
 low grade “sterile” inflammation, as evidenced by increase plasma concentration of inflammatory
markers;
 3) In addition to frailty, inflammation also plays a key role in the pathogenesis of insulin resistance;
 4) Metformin has both insulin sensitizing and anti-inflammatory properties, and;
 5) Our analyzed clinical administrative data from 2,415 adult veterans with diabetes shows that those who
 were taking metformin as monotherapy were at 34% reduced risk of becoming frail compared to patients
 taking sulfonylureas.
We hypothesize that metformin will lead to reduced inflammation and insulin resistance present in
older glucose-intolerant subjects and that these changes will consequently prevent the onset and/or
progression of frailty in this sub-population of older adults.
We propose to study glucose intolerant subjects, a population which encompasses approximately one-third of
older adults, and is most likely to benefit from metformin. To our knowledge, this research will be the first to
study a potential intervention targeted toward a central mechanism involved in the etiology of frailty. We will
also assess potential molecular mechanisms (insulin signaling, AMPK signaling, etc.) as potential cellular
defects in frailty that are alleviated by metformin. Because of the enormous costs associated with frailty (both
personal and economic), a treatment that prevents or delays frailty, even in a sub-population of older adults,
would have a major positive impact in our society.

## Key facts

- **NIH application ID:** 10598726
- **Project number:** 3R01AG052697-05S2
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Sara Elyse Espinoza
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $386,951
- **Award type:** 3
- **Project period:** 2017-06-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10598726

## Citation

> US National Institutes of Health, RePORTER application 10598726, Metformin for Preventing Frailty in High Risk Older Adults (3R01AG052697-05S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10598726. Licensed CC0.

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