This trial is active, not recruiting.

Condition prediabetes
Treatments metformin, placebo
Phase phase 1/phase 2
Sponsor VA Office of Research and Development
Collaborator Oregon Health and Science University
Start date April 2014
End date August 2018
Trial size 120 participants
Trial identifier NCT01804049, CLIN-019-12S


Sarcopenia is the loss of muscle mass, strength and function with aging and is associated with increased disability, falls and fractures. Older adults with diabetes and prediabetes are insulin resistant and have a higher risk of developing sarcopenia. This study examines the use of metformin, an antidiabetic drug, for preventing the development of sarcopenia in older adults with prediabetes.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Intervention model parallel assignment
Masking double blind (subject, investigator)
(Placebo Comparator)
60 participants will be randomized to placebo pills.
One placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study.
(Active Comparator)
60 enrolled participants will be randomized to metformin.
metformin Glucophage
Metformin will be given at a dose of 850 mg orally once daily for 1 month with titration up to 850 mg orally twice daily for the remainder of the study.

Primary Outcomes

Change in total and appendicular lean mass
time frame: 3 years

Secondary Outcomes

Change in physical performance
time frame: 3 years
Change in muscle characteristics
time frame: 6 months

Eligibility Criteria

Male or female participants at least 65 years old.

Inclusion Criteria: - The investigators will enroll 120 sedentary, weight-stable, ambulatory Veterans aged 65 years and older with prediabetes identified with fasting glucose values 100 mg/dL or greater but under 126 mg/dL with no use of diabetes medications. - Participants must demonstrate that they are able to ambulate 400 meters without assistance. Exclusion Criteria: - Chronic medical conditions affecting muscle mass or function like active non-skin cancer and hypogonadism - Medications affecting muscle mass or function like glucocorticoids and androgen/antiandrogens - Contraindications to metformin such as renal dysfunction defined as creatinine >= 1.5 mg/dL for men or >=1.4 mg/dL for women or eGFR<60 mL/min; liver dysfunction defined as ALT>48 U/L, AST>41 U/L or AlkPhos>141U/L; B12 deficiency defined as B12 level <180 pg/dL; congestive heart failure; known hypersensitivity to metformin; excessive alcohol intake (average of 2 or more alcoholic beverages/day over a month) For the muscle biopsy substudy, additional exclusion criteria include: - Conditions that include bleeding risk such as the use of warfarin, clopidogrel/ticlopidine, aggrenox, dabigatran or anagrelide; laboratory results showing platelets<150 billion/L or INR>1.2 or aPTT>36 seconds - Allergy to lidocaine

Additional Information

Official title Metformin and Muscle in Insulin-resistant Older Veterans
Principal investigator Robert F Klein
Description The proposed study utilizes clinical and translational research approaches to study sarcopenia. Sarcopenia is common in older adults and is associated with decreased strength, increased disability, falls and fractures. There are currently few interventions to prevent or treat sarcopenia and a poor understanding of the mechanisms for sarcopenia. Given the growing number of Veterans over the age of 65, studies to prevent sarcopenia and resulting disability are important for the health, independence and well-being of this population. The investigators' preliminary studies have shown that older adults with diabetes have an accelerated loss in muscle mass and gait speed, except when treated with metformin. Older adults with prediabetes also have a greater decline in muscle mass and higher incidence of disability. Therefore, this study further investigates these findings by addressing the following aims: (1) to determine whether metformin can prevent the loss in muscle mass and physical performance and (2) to examine changes in muscle histologic characteristics associated with metformin treatment in older adults with prediabetes.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by VA Office of Research and Development.