Metformin for Preventing Frailty in High-risk Older Adults

July 31, 2025 updated by: Sara E Espinoza, The University of Texas Health Science Center at San Antonio
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. The investigators 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Physical frailty is a geriatric syndrome that leads to poor health outcomes such as falls, disability, institutionalization, and death. The prevalence of frailty is estimated to be 7-15% among community-dwelling older U.S. adults. The associated costs of frailty were estimated to be more than $18 billion in 2000 and these will continue to increase over the next two decades. Thus, an increasingly frail older population will have major implications for the demand for health care services, including hospital usage, home care, and long-term care.

Data from several studies have suggested strong roles for diabetes and insulin resistance, which are associated with increased inflammation, in the physiological basis of frailty. The investigators' recent epidemiological research with a community-based population of older adults showed that diabetes was the most significant predictor of frailty onset and worsening over time. While the importance of frailty and its impact on an aging U.S. society have been widely recognized, to date there are no effective interventions to prevent or treat frailty. Therefore, the major goal of this study is to test a drug with insulin-sensitizing and anti-inflammatory properties, such as metformin, as a novel intervention for frailty prevention.

The investigators 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. Subjects with impaired glucose intolerance will be enrolled in this study because this group encompasses approximately 1/3rd of the older population, this group is at increased risk for developing diabetes and frailty, and is the most likely to benefit from a potential anti-inflammatory and insulin-sensitizing intervention.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
141

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Texas
      • San Antonio, Texas, United States, 78229
        • University of Texas Health Science Center at San Antonio

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

65 years to 90 years (Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Men and women
  • All ethnic groups
  • Age 65 and older
  • Community-dwelling
  • Pre-diabetic based on oral glucose tolerance test with 2 hour values of 140 - 199 mg/dL after an oral glucose load, and no diagnosis of diabetes in the past 12 months
  • Subjects must have the following laboratory values: Hematocrit ≥ 33%, aspartate aminotransferase < 2 X upper limit of normal, alanine aminotransferase < 2 X upper limit of normal, alkaline phosphatase < 2 X upper limit of normal, normal urinalysis (no clinically significant white blood cells, red blood cells or bacteria), platelets ≥ 100,000, prothrombin time < 15 seconds and partial thromboplastin time < 40 seconds, glomerular filtration rate (GFR) ≥ 45ml/min and urine protein ≤ 100 mg/dL by lab urinalysis.

Exclusion Criteria:

  • Characterized as frail, defined as the presence of 3 or more of: 1) weak hand grip strength, 2) slow walking speed, 3) low physical activity, 4) unintentional weight loss of ≥ 10 pounds over the past year, 5) self-reported exhaustion
  • Resident of nursing home or long-term care facility
  • Subjects with diabetes with range fasting glucose in diabetes range (≥ 126 mg/dL), or 2-hour glucose within diabetes range on OGTT (≥ 200 mg/dL).
  • Subjects taking drugs known to affect glucose homeostasis
  • Untreated depression or Geriatric Depression Scale (GDS) score on 15-item scale >7
  • Diagnosis of any disabling neurologic disease Parkinson's Disease, Amyotrophic Lateral Sclerosis, multiple sclerosis, cerebrovascular accident with residual deficits (muscle weakness or gait disorder), severe neuropathy, diagnosis of dementia or Mini-mental State Exam (MMSE) score <24, cognitive impairment due to any reason such that the patient is unable to provide informed consent.
  • History of moderate-severe heart disease (New York Heart Classification greater than grade II) or pulmonary disease (dyspnea on exertion upon climbing one flight of stairs or less; abnormal breath sounds on auscultation)
  • Poorly controlled hypertension (systolic >160 mmHg, diastolic >100 mmHg)
  • Peripheral arterial disease (history of claudication)
  • Moderate to severe valvular heart disease
  • Subjects who have been treated with long term (>30 days) systemic steroids, anabolic steroids, growth hormone or immunosuppresants within the last 6 months. Males with a medical history of testosterone deficiency who are on a stable dose of testosterone replacement (for ≥ 3 months) are allowed.
  • Subjects who have been treated with short term (<30 days) systemic steroids, anabolic steroids, growth hormone or immunosuppressants within the last 1 month.
  • Chronic inflammatory condition, autoimmune disease, or infectious processes (e.g., active tuberculosis, Human Immunodeficiency Virus, rheumatoid arthritis, systemic lupus erythematosus, acute or chronic hepatitis B or C)
  • Active tobacco use (within 6 months)
  • Illicit drug use
  • Active malignancy, non-skin
  • Disease or condition likely to cause death within 5 years
  • Hypersensitivity to metformin or pioglitazone
  • Any disease or condition considered to be exclusionary based on the clinical opinion and discretion of the PI

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Metformin
Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated)
Drug: Metformin
Subjects will be randomized to metformin titrated to 1000mg twice daily as tolerated.
Placebo Comparator: Placebo
Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo.
Drug: Placebo
Subjects will randomized to placebo will receive placebo

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Frailty Index Based on Deficit Accumulation
Time Frame: 2 years
Frailty index based on deficit accumulation. The frailty index will be measured based on the presence of several potential deficits, including chronic diseases, conditions, and impairments. Deficits are ascertained from study visit assessments, including medical history, physical examination, physical function, cognitive function, disability, and quality of life. The frailty index score was calculated as the ratio of the number of deficits to the total number of deficits. The total range of the index is 0 to 1, with higher score indicating more frailty. The outcome is the covariate adjusted monthly rate of change in the frailty index over the study period.
2 years
Fried Frailty Phenotype Criteria
Time Frame: Baseline to 2 years
The frailty score will be measured based on the following 5 frailty characteristics: 1) unintentional weight loss of >= 10 pounds in last year at baseline and ≥5% loss of body weight during follow-up; 2) self-reported exhaustion based on the Geriatric Depression Scale item, "Do you feel full of energy?;" 3) muscle weakness based on hand grip strength measurement (standardized cut points are published); 4) slow gait speed based on 10-foot walk (standardized cut points are published); and 5) low physical activity measured in kilocalories/week based on the Minnesota Leisure Time Questionnaire (standardized cut points are published). The Fried frailty score was calculated as the number of frailty characteristics present, each with a score of 0 or 1. The total range of scores is 0-5, with a higher score indicating more frailty. The outcome is the covariate adjusted monthly rate of change in the Fried frailty score over the study period.
Baseline to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
The University of Texas Health Science Center at San Antonio

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Aging (NIA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sara E Espinoza, M.D., Associate Professor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 7, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 7, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 8, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 6, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 7, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 6, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 31, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • HSC20150237H
  • 1R01AG052697-01A1 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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