Metformin for Muscle Health in Older Adults

Overseen By Brenda Northrup

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Utah

Must not be taking: Anticoagulants, Corticosteroids, Estrogen

Disqualifiers: Cardiovascular disease, Diabetes, Cancer, others

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

64 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you cannot participate if you are using anticoagulant therapy or chronic systemic corticosteroids. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug metformin for muscle health in older adults?

Research suggests that short-term metformin use in older adults can improve the function of muscle progenitor cells, which are important for muscle repair and growth. Additionally, metformin may enhance the response to resistance exercise training by altering the muscle's inflammatory environment, potentially improving muscle mass and strength. ^{1 2 3 4 5}

Is metformin generally safe for humans?

Metformin is a commonly used medication for type 2 diabetes and is generally considered safe for humans. However, it may not be effective in preventing muscle loss in older adults, and its effects on muscle health need further study. ^{1 4 6 7 8}

How does the drug metformin differ from other treatments for muscle health in older adults?

Metformin is unique because it is traditionally used as an antidiabetic drug but is being explored for its potential to improve muscle health in older adults by enhancing muscle response to resistance training and preventing muscle damage from inactivity. Unlike other treatments, metformin may also influence muscle tissue inflammation and promote healthy aging. ^{1 2 5 9 10}

What is the purpose of this trial?

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.

Research Team

Micah Drummond

Principal Investigator

University of Utah

Eligibility Criteria

This trial is for healthy older adults aged 60 and above who can consent to participate. They must not have serious health issues like uncontrolled diseases, recent cancer (except basal cell carcinoma), kidney or liver disease, respiratory problems, cardiovascular conditions, or be on certain medications like anticoagulants.

Inclusion Criteria

You are living independently before being admitted.

Ability to sign informed consent

I am 60 years old or older.

Exclusion Criteria

I have a history of heart disease.

I have vascular disease or risk factors like high blood pressure, obesity, or diabetes.

You are unable to stop smoking for the entire study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Metformin Run-in

Participants receive metformin incrementally to reach a clinical dose of 2 grams per day over a 2-week period

2 weeks

Daily visits (in-person or virtual)

Bed Rest

Participants undergo 5 days of bed rest while receiving metformin or placebo to assess changes in insulin sensitivity and muscle size

5 days

Continuous monitoring during bed rest

Recovery

Participants are monitored for recovery of muscle size, strength, and insulin sensitivity after bed rest

7 days

Regular assessments (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Metformin
• Placebo

Trial Overview The study tests if Metformin helps maintain muscle and metabolic health in bedridden older adults. Participants will either receive Metformin or a placebo while undergoing bed rest. Some participants will only take the assigned treatment during a two-week run-in period before bed rest.

Participant Groups

Group I: Metformin (Bed Rest) Experimental Treatment 1 Intervention

Metformin will be given to participants incrementally during a 2 week run in period such that they will receive the clinical dose (2 grams per day). During bed rest, participants will be given 1 gram of metformin two times a day (morning and evening). This dosage and frequency will occur during four consecutive days of bed rest.

Group II: Metformin (2 week run-in only) Experimental Treatment 1 Intervention

Metformin will be given to participants incrementally during a 2 week run in period such that they will receive the clinical dose (2 grams per day). These participants will not participate in the bed rest portion of the protocol.

Group III: Placebo (2 week run-in only) Placebo Group 1 Intervention

Placebo will be given to participants incrementally during a 2 week run in period such that they will receive the same amount of pills as the experimental group. These participants will not participate in the bed rest portion of the protocol.

Group IV: Placebo (Bed Rest) Placebo Group 1 Intervention

Placebo will be given to participants incrementally during a 2 week run in period such that they will receive the same amount of pills as the experimental group. During bed rest, participants will be given the same amount of pills and given at the same time of day (morning and evening) as the experimental group. This strategy will occur during four consecutive days of bed rest.

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Findings from Research

Insulin therapy does not effectively prevent muscle atrophy in older diabetic patients, highlighting a need for alternative treatments.

While some anti-diabetic drugs like glitazones and AMPK agonists show promise, they may also have unfavorable effects, such as inducing muscle atrophy, particularly in older individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of the antidiabetic drugs on the age-related atrophy and sarcopenia associated with diabetes type II. Cetrone, M., Mele, A., Tricarico, D.[2019]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Effects of the antidiabetic drugs on the age-related atrophy and sarcopenia associated with diabetes type II. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Antecedent Metabolic Health and Metformin (ANTHEM) Aging Study: Rationale and Study Design for a Randomized Controlled Trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Short-term metformin ingestion by healthy older adults improves myoblast function. [2022]

4. China pubmed.ncbi.nlm.nih.gov

[Effect of glucagon-like peptide 1 receptor agonists on body fat redistribution and muscle mass in overweight and obese type 2 diabetic patients]. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Metformin to Augment Strength Training Effective Response in Seniors (MASTERS): study protocol for a randomized controlled trial. [2023]

6. Egypt pubmed.ncbi.nlm.nih.gov

Dulaglutide Protects Mice against Diabetic Sarcopenia-Mediated Muscle Injury by Inhibiting Inflammation and Regulating the Differentiation of Myoblasts. [2023]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Repurposing Drugs for Diabetes Mellitus as Potential Pharmacological Treatments for Sarcopenia - A Narrative Review. [2023]

8. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Effects of Antidiabetic Drugs on Muscle Mass in Type 2 Diabetes Mellitus. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Metformin and leucine increase satellite cells and collagen remodeling during disuse and recovery in aged muscle. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Metformin Treatment Prevents Sedentariness Related Damages in Mice. [2022]