FrailtyPhase 2NCT02570672
Metformin for Preventing Frailty in High-risk Older Adults
A Phase 2 study testing Metformin in people with Frailty, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 65 to 90 years
- Conditions the study is for
- Frailty
- What is being tested?
- Metformin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 141 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2016to 7 Feb 2024
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 to 90 years
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
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.
Read the 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Subjects will be randomized to metformin titrated to 1000mg twice daily as tolerated.
PlaceboDrug
Subjects will randomized to placebo will receive placebo
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Experimental | Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) Receives: Drug: Metformin |
| Placebo | Placebo comparator | Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fried Frailty Phenotype Criteria
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.
Measured: Baseline to 2 years
Secondary outcomes (1)
Frailty Index Based on Deficit Accumulation
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2015 (estimated)
- Study startApr 2016
- Primary completion7 Feb 2024
- Study completion7 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for FrailtyStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 141 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Sara E Espinoza, M.D., Principal investigator, Associate Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02570672
- Sponsor's protocol ID
- HSC20150237H
- Other IDs
- 1R01AG052697-01A1
- Status last verified
- Sep 2026
- First submitted
- 8 Sep 2015
- Last updated
- 15 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Musi N, Wang CP, MacCarthy D, Feng Z, Holmes JT, Suda M, Pirtskhalava T, Aslamy A, Wanagat J, Brooke R, Tchkonia T, Kirkland JL, Horvath S, Espinoza SE. A Randomized Clinical Trial of Metformin to Reduce Frailty in Older Adults with Glucose Intolerance. medRxiv [Preprint]. 2026 Jul 28:2026.07.27.26359055. doi: 10.64898/2026.07.27.26359055.
PubMed 42620010
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin for Preventing Frailty in High-risk Older Adults
- ClinicalTrials.gov ID
- NCT02570672
- Acronym / sponsor ID
- HSC20150237H
- Conditions
- Frailty
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 141 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Apr 2016 (actual)
- Primary completion
- 7 Feb 2024 (actual)
- Study completion
- 7 Feb 2024 (actual)
- First posted
- 7 Oct 2015 (estimated)
- Results
- Posted 6 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Experimental | Drug: MetforminSubjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) |
| Placebo | Placebo comparator | Drug: PlaceboSubjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo. |
Who may qualify
- Ages
- 65 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminSubjects will be randomized to metformin titrated to 1000mg twice daily as tolerated. | Drug | Metformin |
| PlaceboSubjects will randomized to placebo will receive placebo | Drug | Placebo |
Primary outcome
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.
1 secondary outcome
Frailty Index Based on Deficit Accumulation
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42620010Musi N, Wang CP, MacCarthy D, Feng Z, Holmes JT, Suda M, Pirtskhalava T, Aslamy A, Wanagat J, Brooke R, Tchkonia T, Kirkland JL, Horvath S, Espinoza SE. A Randomized Clinical Trial of Metformin to Reduce Frailty in Older Adults with Glucose Intolerance. medRxiv [Preprint]. 2026 Jul 28:2026.07.27.26359055. doi: 10.64898/2026.07.27.26359055.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sara E Espinoza, M.D. principal investigator
Associate Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Frailty, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fried Frailty Phenotype Criteria (time frame: Baseline to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02570672, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.