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I think we have had much debate in various threads about metformin’s pros and cons.
The weight of evidence for the pros of metformin is so great I will ignore anyone disparaging its benefits.
The downsides of taking metformin are small. If you have pre-diabetes or type II diabetes it is still the first drug of choice.
One of the downsides to metformin is it blunts muscle mass gains from exercise. However the key word is blunts, it does not stop muscle mass gains. What they don’t say is that the studies are short-term. Those of us who do resistance training over years of time will not see any significant difference from those who do not take metformin
There are literally thousands of papers explaining the benefits of taking metformin. It probably is one of the best healthspan, if not lifespan, drugs you can take.
For example:
“Metformin has shown a strong antiproliferative effects on colon, pancreatic, breast, ovarian, prostate and lung cancer cells”
“Metformin also inhibits mTORC1 independently of AMPK”
“recent results indicate that the nephroprotective activity against nephrotoxic agents on metformin and its recent good safety records have led researchers to consider the use of this drug more and more in insulin resistant states even before the development of hyperglycemia.”
https://www.sciencedirect.com/science/article/abs/pii/S0165614718301226
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@desertshores i kinda figured this would be your take on this. And not surprisingly, I’ll take the opposite side.
I don’t see any clear evidence that Metformin is of any use in a non diabetic. I may change my mind after the TAME trial gets done but I doubt it. My current opinion is:
Metformin is a mitochondrial poison. (I realize there are many drugs out there that are poisons at the wrong dose.)
It interferes with glucose production in the liver and therefore helps with diabetes.
It may inhibit cancer growth as it is essentially chemotherapy.
It failed the ITP study.
There are better ways for non diabetics to control their glucose levels I.e. exercise, Acarbose, SGLT2.
The basis for its use in longevity was a poorly done study. The science just isn’t there.
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Forget the glucose. Just look at the other benefits.
On mitochondria:
Metformin Can Help Mitochondrial Function - DSM (diabetesselfmanagement.com)
And the article referenced in second link above:
Metformin modulates mitochondrial function and mitophagy in peripheral blood mononuclear cells from type 2 diabetic patients - PMC (nih.gov)
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I want to believe in other benefits of Metformin, I really do. However when I take only 250 mg I cannot leave my house for 2 days sitting mostly in my bathroom. I hate it.
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I know it has negative gastrointestinal effects for some. I cannot take metformin on an empty stomach.
I have two perspectives on metformin.
A few years ago when I was a endurance cycling fanatic (according to my wife), I found metformin significantly reduced my ability to exercise at high levels of effort. Think maximum efforts for 3-10 minutes. Vo2max testing level of effort. I heard Attia say metformin made his lactate go up. That is what my situation felt like. I quit after a month.
Now I do not exercise that hard. I do almost all zone 1-2 (talking pace and a little above). I restarted on metformin after my doctor would not give me acarbose. I find metformin to be no trouble at all now. At first it did send me to the toilet but not anymore. If it keeps me from adding muscle, I don’t care. If it causes me to lose muscle I’ll be irritated. It hasn’t caused me to lose strength or recover more slowly.
If my HbA1c does not improve I’ll be very surprised and annoyed. (I am doing multiple interventions).
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Joseph wrote: I restarted on metformin after my doctor would not give me acarbose.
Cannot believe your doctor would withhold this medication… no negative side effects (breaking wind)… potential health and longevity benefits.
Reminds me how lucky I am… after 2 previous okie-dokey doctors. Finally have a great one. Works with me for my goals.
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She said “it’s an archaic drug that no one prescribes anymore”. She didn’t want to give me metformin either as my A1C was only 5.8. I said, that’s pre-diabetes, right? She said, “just barely …you don’t need to do anything”. I responded that my father died of T2D & heart disease, and that I wanted to avoid that fate. She said she would put in my file that I was feeling afraid because of my family history, and that she agreed to give me metformin to make me feel better.
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Lol, based on that, find a new doctor.
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You would be surprised how many doctors think that way. I don’t change doctors every time I find he has not kept up with the literature. I just self-medicate. 
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What other interventions?
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The rabbit hole goes deep, but here are the big buckets:
Berberine
Exercise everyday
Sleep improvement (no alcohol, no coffee, LDN, stress mgmt)
Green tea
IM fasting & 24 hour fasting
Next blood test in 1.5 mos.
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CTA - covering their asses.
If it were the other way around, and you refused to take a drug, then she is covered by the fact that there was no patient compliance. But if she asks you to take a drug that is not indicated (by her medical judgment), if it results in side effects, her professional insurance is on the line.
Saying that she prescribed to “make you feel better”, is another way of saying the Rx was at the patient’s insistence.
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I listened to part of the video, still not clear what is the key takeaway per Attia on Metformin on the studies cited and his view of it (other than he is undecided).
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That has the advantage of being true.
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It’s hard for me to come up with a reason to take Metformin or Berberine, but impossible to find a reason to take both?
If your HBA1C and blood glucose levels are fine, why take either?
If not, you should take one.
It seems fairly simple to me.
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