Metformin for Preventing Frailty in High-risk Older Adults

NCT02570672 | Completed Phase 2 Results

• 2 other identifiers: HSC20150237H1R01AG052697-01A1
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Frailty

Outcome Measures

Primary Outcomes (2)

• 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.

  2 years

• 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.

  Baseline to 2 years

Study Arms (2)

Metformin

EXPERIMENTAL

Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated)

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Subjects will be randomized to metformin (titrated up to 1000 mg twice daily, as tolerated) vs. placebo.

Drug: Placebo

Interventions

Metformin DRUG

Subjects will be randomized to metformin titrated to 1000mg twice daily as tolerated.

Metformin

Placebo DRUG

Subjects will randomized to placebo will receive placebo

Placebo

Eligibility Criteria

• Age: 65 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Frailty

Interventions

Metformin

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Sara Espinoza
• Organization: UT Health San Antonio

Sara.Espinoza@cshs.org

210 617 5197

Study Officials

• Sara E Espinoza, M.D.

  Associate Professor

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 8, 2015
• First Posted: October 7, 2015
• Study Start: April 1, 2016
• Primary Completion: February 7, 2024
• Study Completion: February 7, 2024
• Last Updated: August 6, 2025
• Results First Posted: August 6, 2025

Record last verified: 2025-05

Locations

US (1)