Metformin why not?

General Discussion
1

Hello,
I’ve mentioned this before and still did not get satisfied conclusion/answer.

I happened to come across a talk by Dr. Nir Barzilai who is a director at anti aging institution. He mentioned about many studies done on positive effects of metformin and covid virus. Basically people who were on metformin had a better outcome with covid virus. covid is virus and so is hbv. They are different but also metformin is an immune modulator as well as it is used for diabetes and even for infertility and god knows what else it is used for. That’s right, it is used for anti aging. So I emailed him if it would be helpful or safe for chronic hep b people to take a small dosage of metformin. He said he doesn’t know. His answers were curt but still nice enough to email me back. I pressed on asking if it is at least safe and he said I guess. Because my liver specialist said no to metformin and Thomas here also advised against it, I’m still on the fence on metformin.

The thing is it takes years to develop a drug and get an approval. Perhaps a decade to get a drug on the market. It’s too long. According to 2022 hep b conference talk, I learned that hepb only gets 1/10th of HIV funding. Hbv is not a priority disease despite the fact that there are more people suffering from hbv than hiv. Besides since there is a vaccine for hbv, we are on the lowest priority.
Anyway in short, we are not getting what we need. This is why I’m insisting in asking non traditional ways of figuring things out.
I’d really appreciate it if someone can convince me if it really is dangerous to take metformin in a small dosage? And was metformin ever explored in part of the hbv treatment? If not, why not? Metformin has been around like 60,70 years and had been used extensively. Only in recent years, due to internet and Dr. Sinclaire talking about reversing the aging, it is getting much attention. So why is it not being tested/used in hbv therapy. Why is that? People with diabetes on metformin live longer than people who don’t have diabetes. Do you find that interesting?

Last year, I posted my concern for high cholesterol as I began entering my 50’s and hit menopause. I thought it was vemlidy that I was taking. Turns out it’s not so much that. I was able to lower my cholesterol with vegan diet. When it wasn’t low enough I did more research. I found it. I did a bloodwork before i began consuming more soy beans and other kinds of beans in my diet. Then I did a bloodwork about a month after and the cholesterol level went down significantly.
that was it. Somehow beans and soy beans boosted by estrogen level which in turn helped with lowering cholesterol.

Another thing I am so annoyed is that it’s not easy for me to convince the doctors to do the bloodwork for no reason because they are expensive and my insurance has limit to what can be covered. Is there a way to get more frequent bloodwork in USA ? Bloodwork helps me to figure out what works and what doesn’t. Without my bloodwork test, I can only guess.

Please convince me that metformin is unsafe to take.
Thank you for your feedbacks!

2

Dear @catcher.007,

As mentioned previously (for anyone who had not seen the old posts), there doesn’t seem to be any benefits to taking metformin in clinical trials investigating this. Links here:

Thomas

3

Thank you Thomas for your comments. I have a few questions.

  1. what does this mean below? is this good or bad?
    By the virtues of preferably hepatocyte distribution and safety profile, collectively, our results suggest that metformin would be potentially clinically helpful as an HBsAg production inhibitor.
    Metformin inhibits hepatitis B virus protein production and replication in human hepatoma cells - PubMed

  2. what does below mean?
    This population-based cohort study investigated the protective effect of statin and metformin against cancer events in patients with HBV infection. Our study demonstrated that either statin or metformin served as independent chemopreventive agents with a dose-response effect in reducing the incidence of cancer with a dose-response effect of the agents and an additive or synergistic effect of combining statin and metformin use in reducing the incidence of many cancers.
    Cancer risk in HBV patients with statin and metformin use: a population-based cohort study - PubMed

  3. And my questions is not whether metformin is beneficial or not for chronic hbv patients. My question is that is metformin harmful if one takes a small dosage of it (for chronic hbv patients) given that person is relatively healthy?

The reason why I keep asking is that this is important for me. If I had listened to the doctors whom I’ve seen for other issues and took their advices without questioning then I’d be on several drugs such as statin which turns out that I don’t really need. I feel like I have to keep pushing for logical reasoning to get the right answer.

Metformin is used for many illnesses but its side effects are longetivity, reversing aging, boosting immune system(super important). I just really want the side effects of its use. Sorry if I sound insistent. Just wanted to see if other people here have explored metformin and I also wanted to hear experts’ advice to see if I can get a confirmation on whether it is safe to take or not- not necessarily beneficial to take.

thank you.

4

Hi @catcher.007,

Just quickly:

  1. The authors are suggesting that there might be a way of using metformin to reduce HBsAg. I think this is over-interpretation by the authors, the therapeutic dose of metformin is in the micromolar range; the dose required to reduce HBsAg in this cell culture model is 1000 times this (millimolar).

  2. This paper shows no significant effect for liver cancers “Patients taking only metformin had risk-adjusted HRs of 0.97 (95% CI, 0.84-1.14) for liver cancer” in this cohort.

  3. Any medication can be harmful, but the principle that medicine takes is whether those potential harms are outweighed by the potential benefits. If the benefits are 0, then they will never outweigh any harm no matter how small. On top of this, there are described side-effects of metformin (Metformin (Oral Route) Side Effects - Mayo Clinic):

More common

  1. Abdominal or stomach discomfort
  2. cough or hoarseness
  3. decreased appetite
  4. diarrhea
  5. fast or shallow breathing
  6. fever or chills
  7. general feeling of discomfort
  8. lower back or side pain
  9. muscle pain or cramping
  10. painful or difficult urination
  11. sleepiness

Less common

  1. Anxiety
  2. blurred vision
  3. chest discomfort
  4. cold sweats
  5. coma
  6. confusion
  7. cool, pale skin
  8. depression
  9. difficult or labored breathing
  10. dizziness
  11. fast, irregular, pounding, or racing heartbeat or pulse
  12. feeling of warmth
  13. headache
  14. increased hunger
  15. increased sweating
  16. nausea
  17. nervousness
  18. nightmares
  19. redness of the face, neck, arms, and occasionally, upper chest
  20. seizures
  21. shakiness
  22. slurred speech
  23. tightness in the chest
  24. unusual tiredness or weakness

Rare

  1. Behavior change similar to being drunk
  2. difficulty with concentrating
  3. drowsiness
  4. lack or loss of strength
  5. restless sleep
  6. unusual sleepiness
1 Like
5

Thank you Thomas.

  1. I’m not sure about the first article. You mentioned about the dosage of metformin is 1000 times… I don’t understand what that means. I’m assuming you are noting the high dosage for the study that was done with a promising headline of metformin usage?

  2. the conclusion for the second article seems to go against what you have commented on so I must be confused not understanding the data.

  3. you are right in that if the there is no benefit in taking metformin then why take the chance of potential harms. But that is if you are considering only the negative side effects that come with metformin. But the possible benefits are great (potentially outweigh the negatives) if they are indeed true.

I guess I’m reading unbelievably potentially positive side effects than the small minor negative side effects with consumption of metformin that is making me keep pushing for the answers. For instance, I would take the nausea in exchange for a stronger immune system. Besides the nausea only lasts for a few days and if it continues, you stop taking it.
It is very confusing for regular people like me when there are many articles/ studies done and podcast by the experts saying positive benefits and the negative side effects on one thing. Hence why I have asked on this platform.
I guess I will continue to be on the fence with metformin at this point as I am not convinced that it will be safe to take for hbv patients.

Anyway thank you for your comments.

6

Hi @catcher.007,

  1. When you take metformin the amount in your blood is about 1 micromolar. In the paper you cite, the researchers only see a reduction (50%) when 1000 micromolar of metformin is added to the cells. So either it will have no effect, or you have to take so much metformin that some of the side-effects described above become more likely, frequent, or severe.

  2. The authors in that paper show that there is a slight reduction in non-liver cancers (Relative risk of 0.75), but not liver cancers. If you look in Table 2 in fact, the rate of liver cancer is significantly higher in people using metformin (Hazard ratio of 1.25). This suggests that the metformin isn’t acting against the Hep B at all (which is the major cause of liver cancers), but might be affecting other pathways to prevent cancers of other sorts (which is what the conclusion is referring to). This could be due to a better management of their diabetes making cancers less likely or something else completely.

  3. Again, there is no evidence that metformin is helpful at all for Hepatitis B or related diseases.

Thomas

7

Thank you for your interpretation.

1 Like