Metformin for Muscle Weakness

Overseen By Rebekah Drummond

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: University of Utah

Must not be taking: Anticoagulants, Corticosteroids, Androgens, Estrogens

Disqualifiers: Cardiovascular, Endocrine, Kidney, Vascular, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether metformin, a common diabetes medication, can help older adults regain muscle strength after a period of disuse. The goal is to determine if metformin can reduce muscle weakness and improve recovery, potentially lowering the risk of falls and aiding in maintaining independence. Participants will receive either metformin or a placebo for two weeks during the recovery phase. Those who are generally healthy, live independently, and have good upper body strength may be suitable candidates. As an Early Phase 1 trial, this research aims to understand how metformin works in people, offering participants a chance to contribute to groundbreaking insights.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using anticoagulant therapy, chronic systemic corticosteroids, androgens, growth hormone, or estrogen products (except topical ones).

Is there any evidence suggesting that metformin is likely to be safe for humans?

Research shows that metformin is usually easy for people to take. This widely used medicine for type 2 diabetes has been available for many years. Studies have found that metformin can help older adults improve grip strength and physical performance, suggesting it might be safe and beneficial for muscle health.

However, some people may experience side effects such as fatigue, muscle weakness, and tingling in their hands and feet. It's important to note that these side effects don't occur in everyone.

In summary, while metformin has been used for a long time and is often considered safe, it can have side effects like any medication. Participants should consider these factors when deciding to join a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for muscle weakness, which often involve physical therapy and nutritional supplements, Metformin is being explored for its potential to aid muscle recovery. Researchers are excited about Metformin because it's traditionally used for diabetes but may have a unique effect on muscle metabolism and inflammation. This could lead to faster recovery times following muscle immobilization. If successful, Metformin could offer a novel approach by enhancing muscle strength and function in a way existing treatments don't.

What evidence suggests that metformin might be an effective treatment for muscle weakness?

Research has shown that metformin, which participants in this trial may receive, can improve muscle mass and strength in several ways. Studies have found that it boosts grip strength and physical performance, especially in older adults. Metformin strengthens the connection between nerves and muscles, reducing muscle weakness. It may also aid muscle recovery by enhancing cell function and slowing harmful aging processes in cells. While metformin is well-known for treating diabetes, these findings suggest it could also benefit muscle health. ^{1 3 5 6 7}

Who Is on the Research Team?

Micah Drummond

Principal Investigator

University of Utah

Are You a Good Fit for This Trial?

This trial is for older adults who are generally healthy, can walk with assistance if needed, and live independently. They should have a body mass index (BMI) less than 30, not be considered frail according to specific scales, and must be aged 60 or above.

Inclusion Criteria

I can use crutches or a walker with my upper body strength.

I am in good health, can walk on my own, and live independently.

Your body mass index (BMI) is less than 30.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Immobilization

Participants undergo single leg immobilization to induce muscle disuse atrophy

2 weeks

Recovery

Participants receive metformin or placebo during the recovery phase to improve muscle regrowth

2 weeks

Daily oral administration

Follow-up

Participants are monitored for muscle recovery and function after the treatment phase

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The study tests whether Metformin helps improve muscle regrowth in older adults after periods of not using their muscles which leads to weakness. Participants will either receive Metformin or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Metformin Experimental Treatment 1 Intervention

Metformin pills will be given orally and daily during the 2-week recovery period following single leg immobilization Metformin will be titrated up to a dose 2g/day. 1g dose (two 500 mg pills) will be taken in the morning and a 1g dose will be taken in the evening. This will take place over each day for 14 days during the recovery period.

Group II: Placebo Placebo Group 1 Intervention

Placebo pills will be given orally and daily during the 2-week recovery period following single leg immobilization. Two pills will be taken in the morning and two pills will be taken in the evening. This will take place over each day for 14 days during the recovery period.

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+

Published Research Related to This Trial

In a small-scale study of 40 ambulatory adult patients with myotonic dystrophy, metformin treatment led to a significant improvement in mobility, as measured by the 6-minute walk test, with the treated group walking an average of 32.9 meters further than the placebo group (P < 0.05).

Metformin was associated with an increase in total mechanical power during walking, indicating a positive effect on gait, although the treatment also resulted in mild-to-moderate gastrointestinal side effects, highlighting the need for further research in larger trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved mobility with metformin in patients with myotonic dystrophy type 1: a randomized controlled trial. Bassez, G., Audureau, E., Hogrel, JY., et al.[2019]

The combination of oral glycine and metformin with intravenous phosphorodiamidate morpholino oligomer (PMO) significantly enhances PMO activity and dystrophin restoration in dystrophin/utrophin double knock-out mice, leading to improved muscle function and extended lifespan without adverse effects.

This study suggests that using glycine and metformin together could improve the delivery and effectiveness of PMO treatments for Duchenne muscular dystrophy (DMD) patients, potentially accelerating clinical trials for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardio-respiratory and phenotypic rescue of dystrophin/utrophin-deficient mice by combination therapy. Lin, C., Han, G., Jia, L., et al.[2023]

Glumetz (M-ER) is a newly approved extended-release formulation of metformin that provides effective and sustained glycemic control with once-daily dosing, showing similar bioavailability to immediate-release metformin taken twice daily.

In clinical trials lasting 24 weeks, M-ER demonstrated good efficacy and was well tolerated, with continued glycemic control maintained in an additional 24-week open-label extension study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical development of metformin extended-release tablets for type 2 diabetes: an overview. Schwartz, SL., Gordi, T., Hou, E., et al.[2013]

Metformin, primarily used for treating type 2 diabetes, may enhance muscle glycogen replenishment at high altitudes, suggesting potential benefits for athletes.

There is limited information on the safety risks of using metformin in healthy individuals, highlighting the need for further research on its misuse in non-diabetic populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin for high-altitude performance? Burtscher, M.[2019]

Metformin (MET) enhances the expression of important proteins like PGC-1α and utrophin A in both cultured muscle cells and mdx mice, which are models for Duchenne muscular dystrophy (DMD).

The study suggests that MET's ability to modulate these proteins could make it a promising therapeutic option for DMD, highlighting the need for further research into AMPK activators in muscle disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin increases peroxisome proliferator-activated receptor γ Co-activator-1α and utrophin a expression in dystrophic skeletal muscle. Ljubicic, V., Jasmin, BJ.[2015]

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]

Metformin extended release (ER) provides effective glycaemic control with once-daily dosing, showing similar effectiveness to twice-daily dosing of immediate-release formulations over a 24-week period in clinical trials.

The metformin ER formulation was well tolerated at doses of 1500 and 2000 mg/day, with no increase in adverse events, indicating its safety for patients managing their blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metformin extended release for the treatment of type 2 diabetes mellitus. Schwartz, SL., Wu, JF., Berner, B.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8818615/

Metformin induces muscle atrophy via HDAC6 & FoxO3a Our results demonstrate that metformin treatment impairs muscle function through the regulation of myostatin in skeletal muscle cells via AMPK‐FoxO3a‐HDAC6 ...

2. goodrx.com goodrx.com/metformin-er-glucophage-xr/glucophage-xr-vs-glumetza-vs-fortamet?srsltid=AfmBOorvoDamzlNXwd07NPTmubCOQUCtvo2x6XySOq18Ix1eLTfOneDf

Metformin Brands: Glucophage XR vs. Glumetza vs. Fortamet Signs of anemia include low energy, muscle weakness, low appetite, and tingling sensations in your hands and feet. This can worsen nerve pain for some people.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167494324002632

Metformin Stabilizes Neuromuscular Junction in Older Adults Metformin improves grip strength and physical performance in old age. ... Degradation of neuromuscular junction contributes to muscle weakness but not ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10621799/

Mechanisms and effects of metformin on skeletal muscle ... Interestingly, along with its hypoglycemic effect, metformin can also improve skeletal muscle mass and strength through different mechanisms, thereby delaying ...

5. diabetesjournals.org diabetesjournals.org/diabetes/article/73/11/1875/157146/Effect-of-Metformin-on-Peripheral-Nerve-Morphology

Metformin Effect on Peripheral Nerve in Type 2 Diabetes Diabetic peripheral neuropathy (DPN) occurs in ∼50% of individuals with type 2 diabetes and causes muscle weakness, neuropathic pain, and ...

6. goodrx.com goodrx.com/metformin-er-glucophage-xr/glucophage-xr-vs-glumetza-vs-fortamet?srsltid=AfmBOorLrh-xe5DGhkeheozLmR7DVYG_-5C1HkDg03_jWJsrk_inrHa9

Metformin Brands: Glucophage XR vs. Glumetza vs. Fortamet Signs of anemia include low energy, muscle weakness, low appetite, and tingling sensations in your hands and feet. This can worsen nerve pain for some people.

7. mayoclinic.org mayoclinic.org/drugs-supplements/metformin-oral-route/description/drg-20067074

Metformin (oral route) - Side effects & dosage Metformin is used to treat high blood sugar levels that are caused by a type of diabetes mellitus or sugar diabetes called type 2 diabetes.