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

Trial Summary

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).

What data supports the effectiveness of the drug Metformin for muscle weakness?

Research shows that Metformin improved mobility in patients with myotonic dystrophy type 1, as those treated with Metformin walked further in a 6-minute test compared to those given a placebo. Additionally, Metformin has been shown to enhance muscle function in animal models and may help improve muscle health in conditions like Duchenne muscular dystrophy. ^{1 2 3 4 5}

Is metformin generally safe for humans?

Metformin, used primarily for type 2 diabetes, is generally well-tolerated in humans, with studies showing it is safe at doses of 1500 to 2000 mg/day. However, it should not be used by people with kidney problems. ^{2 3 4 6 7}

How does the drug metformin differ from other treatments for muscle weakness?

Metformin is unique because it not only helps with diabetes but also shows potential in improving muscle function by activating AMPK, a protein that helps remodel muscle cells. Unlike other treatments, it has been shown to improve mobility in conditions like myotonic dystrophy and may enhance the effectiveness of other therapies for muscular dystrophies. ^{1 2 3 4 5}

What is the purpose of this trial?

A hallmark of aging is an impaired ability to adequately recover following a stressor, such as muscle disuse, resulting in muscle fibrosis and weakness thereby increasing the risk for falls and loss of independence. Mechanistic-based therapeutic strategies to enhance muscle recovery in older adults do not exist. Metformin has been implicated to have positive effects on muscle size and function through non-glycemic mechanisms. Metformin has been shown to enhance macrophage function and lessen cellular senescence burden by targeting SASP in a variety of muscle interstitial cells. However, the role of metformin to improve muscle recovery in older adults following disuse atrophy through immunomodulating and senomorphic mechanisms have not been examined. Therefore, the purpose of this study is to conduct a randomized, double blind, placebo-controlled clinical trial in older adult participants to determine if short-term metformin delivery (vs placebo) during the recovery phase following disuse atrophy can improve muscle regrowth.

Research Team

Micah Drummond

Principal Investigator

University of Utah

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Improved mobility with metformin in patients with myotonic dystrophy type 1: a randomized controlled trial. [2019]

2. 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]

3. Australia pubmed.ncbi.nlm.nih.gov

Metformin for high-altitude performance? [2019]

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

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

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

Cardio-respiratory and phenotypic rescue of dystrophin/utrophin-deficient mice by combination therapy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Clinical development of metformin extended-release tablets for type 2 diabetes: an overview. [2013]

7. England pubmed.ncbi.nlm.nih.gov

Metformin extended release for the treatment of type 2 diabetes mellitus. [2019]