Common Diabetes Medication Reverses Pulmonary Fibrosis in Mouse Model of Disease

Common Diabetes Medication Reverses Pulmonary Fibrosis in Mouse Model of Disease

A common oral medication for type 2 diabetes called metformin was seen to quickly reverse pulmonary fibrosis in a mouse model of the disease and lessen fibrosis in lung tissue of PF patients, a study reports, adding that similar compounds might have similar benefits.

The research, “Metformin reverses established lung fibrosis in a bleomycin model,” appeared in the journal Nature Medicine.

Lung fibrosis, or scarring, is a result of abnormal repair to tissue injured by infections, autoimmune diseases, occupational and environmental exposure to toxic substances, radiation or chemotherapy. It also can stem from causes unknown, as is the case of idiopathic pulmonary fibrosis (IPF).

Tissue repair is regulated by cellular metabolism, which requires the proper functioning of an enzyme called AMPK (short for adenosine monophosphate (AMP)-activated protein kinase), a key sensor of a cell’s energy state and a metabolic regulator.

To better understand the link between AMPK and PF, researchers with The University of Alabama at Birmingham used lung tissues from IPF patients, mice in a model of lung fibrosis, and mouse lung fibroblasts — cells that produce proteins implicated in wound-healing and fibrosis.

They found AMPK activity to be lower-than-usual in fibrotic regions of lung tissue from the IPF patients, particularly in myofibroblasts — cells that, similar to fibroblasts, release collagen during the development of fibrosis. Lower AMPK activity is associated with metabolically active and apoptosis-resistant myofibroblasts, changes that enhance and promote fibrosis. [Apoptosis refers to “programmed” cell death, as opposed to cell death caused by injury; it is used to rid an organism of cells no longer needed or damaged.]

Compounds that activated AMPK in these tissue myofibroblasts showed lesser fibrosis, better mitochondrial production (a cell’s energy source) and normal sensitivity to apoptosis.

Metformin, a widely used treatment for non-insulin-dependent diabetes, is known from previous studies to have anti-fibrotic effects on multiple organs. Metformin is also an activator of AMPK.

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Activating AMPK with metformin or with another AMPK-activator  — one called Aicar — eased fibrosis and increased the production of mitochondria in IPF patients’ myofibroblasts.

In mice with bleomycin-induced lung injury — probably the most used animal model to study PF — this disease is known to resolve over time. But, “the mechanisms promoting resolution are not well understood,” the researchers wrote.

They tested whether metformin could accelerate fibrosis resolution in the bleomycin-affected mice. These animals were given  metformin starting at three weeks after lung injury and continuing for another five weeks. Results showed faster resolution of well-established fibrosis.

Of note, a group of mice genetically altered not to have the AMPK enzyme did not show this benefit, indicating that metformin and its potential benefits were AMPK-dependent.

“These studies implicate deficient AMPK activation in non-resolving, pathologic fibrotic processes,” the researchers wrote.

“Additionally, we provide proof-of-concept that activation of AMPK by metformin or other pharmacologic agents that activate these pro-resolution pathways may be a useful therapeutic strategy for progressive fibrotic disorders,” they added.

21 comments

    • Timothy Middleton says:

      This news is so exciting we all will sign up immediately but I have to think that I know some of us are already taking metformin for one of our many ailments. I don’t have pre or diabetes so I currently am not. If the people taking here are and still haven’t had they’re PF reversed then what’s wrong? My pulmonologist was exited about this news though and they’re usually calm and not too hype because they know the let downs. So that’s a good sign for me.

  1. Kathy Ann says:

    My husband takes Metformin for his Type 2 Diabetes – – surly there are other diabetics that also have IPF – – wonder how they are doing – maybe they would have to take more ????

  2. Peter Blake says:

    I have type 2 and have been on metformin for 8 years,I was diagnosed with PF 6 years ago my PF is slowly progressing. Although perhaps it would have been faster if I was not on metformin I should up my dose from 2 tablets a day to 4. I wonder how much they give mice to turn back the disease ?

  3. Beth Mackie says:

    My husband has type 2 diabetes and has been on metformin for over ten years and currently takes two pills twice a day. His IPF is progressing more rapidly now and it is three years since initial diagnosis. He also turned 80 this year, this report does however provide hope for others.

  4. Steven says:

    Metformin in its current state has a dose limit recommendation of 2000 mg per day. Higher than that and patients most likely experience some of the unpleasant side-effects.

    Yes it would be good to know what exactly was given to the mice since their bodies are tiny…

  5. Mike Daniels says:

    I would like more information on this. Preferably dosage for adult 72 with body weight of 225. I am diabetic and can adjust for metformin.
    Thanks

  6. Timothy Middleton says:

    I hope the FDA allows them to fast track this study. We need to invest in the maker of metformin. I invest in things I believe. This news needs to be front page of every medical journal.

  7. Michael Lamkin says:

    I’m not diabetic but would be willing to try anything that has real promise as an effective treatment. I was told I had ILD a couple of years ago and then I was recently told I had IPF. I almost had to laugh when the doctor asked if I had my affairs (will, medical power of attorney etc.) in order before even telling me there was no cure for IPF and she didn’t go into a lot of detail regarding the disease, but I got the jest of it. She also told me 68 was the cut off age for a lung transplant but my research told me just the opposite, with many people in their 70’s successfully receiving transplants. The biggest obstacle to a transplant is the patients overall health (i.e. Heart, Liver and other organs) and the availability of a lung.
    I just got over 18 months of fighting Valley Fever and I’ve learned the hard way that you must be your own best advocate when it comes to your health. I was in disbelief when I found out how ignorant most doctors (including one who was a pulmonary doctor) were regarding Valley Fever.

  8. Dale Darling says:

    I have an appointment with the University of Michigan Pulmonary Clinic coming us soon, like the 24th of this month. My lung Doctor wanted to send me there for a second opinion from my CT scan and such, you can bet I will be asking them what they know about this Metformin and report back when I can.

  9. Kathy Kucks says:

    I have just been diagnosed with IPF, and I am happy to report that I still have full lung function, so I would be willing to try Metformin to try and slow it’s progress. I am 76 so by the time it worsens I would neither be eligible or wish to have a lung transplant but would be happy to keep a good quality of life for a few years yet.

  10. robert says:

    The most common use of Metformin is DM, but there are other uses. At the wall mart it is $4 a month. Any MD. NP.PA can order it for these other reasons. We are terminal let us do it.

  11. Gwen Johnson says:

    This was a very informative and interesting article. I am certainly going to look into this further. Was diagnosed this year with PF but have been suffering from ILD for the past two years. I just turned 79.

  12. James Pillows says:

    I have been taking metformin for several years was diagnosed with IPF in 2015 and started on OFEV. The metformin has not seemed to slow my IPF any that is noticeable . My decline is not effecting me in an alarming way. I am 85 years old live by myself do everything myself and am able to travel. I am a mentor for the OFEV drug and will be going to Chicago in Sept for a summit on OFEV which I am excited about. If there are any new things happening I would love to hear about them.

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