Clinical trial NCT01804049: Metformin and Muscle in Insulin-resistant Older Veterans
Official title: Metformin and Muscle in Insulin-resistant Older Veterans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Prediabetes
Keywords: metformin
muscle
insulin resistance
sarcopenia
older adults
impaired fasting glucose
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Oregon Health and Science University
First posted: 2013-03-05
Enrollment: 120
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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 estimated glomerular filtration rate (eGFR)\<60 mL/min; liver dysfunction defined as alanine aminotransferase (ALT)\>48 U/L, aspart aminotransferase (AST)\>41 U/L or alkaline phosphatase (AlkPhos)\>141 U/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 international normalized ratio (INR)\>1.2 or activated partial thromboplastin time (aPTT)\>36 seconds
* Allergy to lidocaine

Primary outcomes:
measure: Change in Total Lean Mass From Baseline
timeFrame: 3 years
Secondary outcomes:
measure: Change in Physical Performance - 400 Meter Walk Speed
timeFrame: 3 years
measure: Change in Muscle Characteristics
timeFrame: 6 months
Other outcomes:
Locations:
city: Portland
country: United States
facility: VA Portland Health Care System, Portland, OR
state: Oregon
Study officials:
affiliation: VA Portland Health Care System, Portland, OR
name: Robert F Klein
role: PRINCIPAL_INVESTIGATOR
References: