Role of Metformin on Muscle Health of Older Adults

  • End date
    Apr 30, 2023
  • participants needed
  • sponsor
    University of Utah
Updated on 7 July 2022
bed rest
Accepts healthy volunteers


Muscle atrophy and insulin resistance are common after bed rest in healthy older adults. Metformin treatment has been shown to improve insulin sensitivity and attenuate muscle loss in insulin resistance adults though the mechanisms are not fully known. Metformin used as a preventive strategy to maintain muscle and metabolic health in bed ridden older adults has not been investigated.


Hospitalizations for disease, injury, and/or surgery in older adults are likely to impair physical mobility and, therefore, the older adults capacity to be physically active both during hospitalization and beyond. The resulting sedentary lifestyle is likely to be accepted as the "new normal", ultimately increasing the risk of skeletal muscle and metabolic dysfunction (e.g. insulin resistance and sarcopenia).

Muscle atrophy and insulin resistance are an unfortunate consequence with disuse in older adults. We have observed with our bed rest studies in healthy older adults that in addition to muscle and metabolic changes, we notice increased skeletal muscle inflammation, impaired glucose uptake signaling and an upregulation of enzymes related to de novo ceramide biosynthesis. The accumulation of ceramide, a toxic lipid intermediate, can disrupt glucose homeostasis and impair muscle growth. Metformin treatment has been shown to improve insulin sensitivity and attenuate muscle loss in insulin resistant adults through a mechanism that may involve ceramide synthesis. Metformin used as a preventive strategy to maintain muscle and metabolic health during a period of physical inactivity in older adults has not been investigated.

A separate group of participants for the 2-week Metformin Run-in Period, independent of the bed rest and recovery study will also be recruited. All study procedures will be the same as the 2-week Run-In period within the full protocol.

We hypothesize that metformin treatment in healthy older adults during bed rest would attenuate inflammation, insulin resistance, and thigh muscle loss and changes in lipid accumulating in muscle. We also hypothesize that elevated skeletal muscle ceramide levels, is central to the development of insulin resistance with bed rest in older adults.

Therefore, we have proposed to conduct a clinical study in older adults to:

  1. Test if daily metformin treatment (vs placebo) during 5d of bed rest in older adults would attenuate intramuscular ceramide accumulation (lipid accumulation), insulin resistance (euglycemic-hyperinsulinemic clamp), and loss in thigh muscle lean mass. We would also like to determine if 5-days of bed rest in older adults within the placebo group increases skeletal muscle ceramide concentrations and whether these are in turn associated with insulin resistance.
  2. Test if daily metformin treatment (vs placebo) during 5d of bed rest in older adults would improve skeletal muscle glucose uptake cell signaling, reduce skeletal muscle inflammation and ceramide biosynthesis signaling.
  3. Determine if muscle ceramides and insulin resistance return to baseline levels following 7 days of recovery after bed rest in the placebo group.
  4. Determine if metformin given over a 2 week period (independent of bed rest) will improve muscle size, strength and insulin sensitivity.
  5. Determine if metformin improves the recovery of muscle size and strength and insulin sensitivity 7 days after bed rest.

These findings will be foundational for future development of treatments to prevent insulin resistance and muscle atrophy in inactive older adults.

Condition Muscle Atrophy, Insulin Resistance
Treatment Placebo, Metformin, Metformin (Bed Rest), Placebo (Bed Rest), Metformin (2 week run-in only), Placebo (2 week run-in only)
Clinical Study IdentifierNCT03107884
SponsorUniversity of Utah
Last Modified on7 July 2022


Yes No Not Sure

Inclusion Criteria

Age 60y and older
Ability to sign informed consent
Free-living, prior to admission

Exclusion Criteria

Personal history of cardiovascular disease
Uncontrolled endocrine or metabolic disease (e.g., hypo/hyperthyroidism, HbA1c ≥6.5%)
Evidence of kidney disease or failure (defined as serum creatinine > 1.5mg/dL)
Vascular disease or risk factors of peripheral atherosclerosis. (e.g., uncontrolled hypertension, obesity, diabetes)
Risk of Deep vein thrombosis including family history of thrombophilia, Deep vein thrombosis, pulmonary emboli, myeloproliferative diseases including polycythemia (Hb>18 g/dL) or thrombocytosis (platelets>400x103/mL)
Use of anticoagulant therapy (e.g., Coumadin, heparin)
Uncontrolled hypertension (e.g. systolic pressure >160 or a diastolic blood pressure > 100)
Cancer or history of successfully treated cancer (less than 1 year) other than basal cell carcinoma
Currently on a weight-loss diet or body mass index > 30 kg/m2
Inability to abstain from smoking for duration of study
HIV or hepatitis B or C
Subjects excluded due to positive screening results, including HIV, hepatitis B or hepatitis C, will be immediately scheduled for counseling and follow-up testing as needed, and will be advised to consult their primary physician
Chronic systemic corticosteroid use (≥ 2 weeks) within 4 weeks of enrollment and for
Subjects with hemoglobin or hematocrit lower than accepted lab values
study duration (intra-articular/topical/inhaled therapeutic or physiologic
History of stroke with motor disability
doses of corticosteroids are permitted). Androgens or growth hormone within 6
A recent history (<12 months) of GI bleed
months of enrollment and for study duration (topical physiologic androgen
Depression [>5 on the 15 items Geriatric Depression Scale (GDS)]
replacement is permitted)
This criteria will only apply to subjects in the bed rest arm
Liver disease (the ratio of serum aspartate aminotransferase to serum alanine aminotransferase 2 times above the normal limit, hyperbilirubinemia) History of respiratory disease
Currently taking estrogen products (topical vaginal products are not exclusionary (e.g. cream))
Recent travel history as defined by 4 hours of travel by airplane in the last week
Any other condition or event considered exclusionary by the PI and faculty physician
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact



Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note