How Metformin works, AKA "Structural basis of mammalian respiratory complex I inhibition by medicinal biguanides"

[wu-lee]

My partner is an academic developmental biologist, and came across this paper on the mechanism of metformin.

https://www.science.org/doi/10.1126/science.ade3332

She says:

It is heavily based on chemistry showing where and how metformin binds to a key enzyme important for processing energy in mitochondria, and this explains how the drug affects the activity of the enzyme and therefore the processing of energy. It is not a readily digestable paper.

She adds:

I think interesting points from the Science paper are not just about explaining how metformin treats diabetes but explaining why it is thought to be so beneficial for other processes (eg cancer) and how the new understanding of it's mode of action might inform efforts to further improve efficacy as a cancer treatment (which so far have been somewhat promising but also a bit disappointing).

However, she found this Twitter thread which puts it into context and gives a summary of current thinking - more digestible! (Linked via Nitter, which is a non-tracking twitter proxy. You don't need an account to read to the end or follow links to other threads!)

stephen o'rahilly (its pronounced O-RA-hill-EEE) (@StephenORahilly)

After decades of confusion and many thousands of papers some real clarity is emerging as to how metformin actually works. Its key sire of action is the intestinal epithelial cell, into which it is selectively very concentrated. There, it impairs mitochondrial oxphos and

nitter.net

 

[Goonergal]

My partner is an academic developmental biologist, and came across this paper on the mechanism of metformin.

https://www.science.org/doi/10.1126/science.ade3332

She says:


She adds:


However, she found this Twitter thread which puts it into context and gives a summary of current thinking - more digestible! (Linked via Nitter, which is a non-tracking twitter proxy. You don't need an account to read to the end or follow links to other threads!)

stephen o'rahilly (its pronounced O-RA-hill-EEE) (@StephenORahilly)

After decades of confusion and many thousands of papers some real clarity is emerging as to how metformin actually works. Its key sire of action is the intestinal epithelial cell, into which it is selectively very concentrated. There, it impairs mitochondrial oxphos and

nitter.net

But what’s your point?

 

[wu-lee]

No particular point - or not yet, maybe after investigating further, but that'll take a while. I am not a biochemist. Possibly someone else may have an interesting comment.

Following the research can be helpful when attempting to fact check some of the claims made about diabetes. (And for anyone else who does this, I'd be interested to compare notes.)

 

[Oldvatr]

I am unable to gain access rights to the PDF. I note in the abstract that they have found that the main binding is to the Co-Q enzyme. This is interesting since I remember from some early research that those on Metformin may need to supplement this. However the reports I saw seemed to show that this supplementation does nothing to change blood sugar levels That advice from those early years does not seem to be common parlance nowadays.

Metformin is known to have at least 3 beneficial effects. The glucose lowering property is actually quite minor. One thing Met does is form a sponge like matrix that captures glucose and sequesters it out in the faeces ( the true bums rush). Met is also associated with reducing insulin resistance (we think it is in the muscle cells, not the adipose tissues but no one seems to have published any evidence for this) It is also associated with a reduction in CVE risk, but again, scant evidence apart from meta studies. This may actually be where the Co-Q enzyme plays a part.

I get the feeling that this study is not actually going to open any new doors.

As regards CoQ10 this is what I found, but it is not a site I recognise

Taking Metformin to Manage Your Diabetes? Make Sure Your Doctor Checks Your Vitamin B12 Levels!

If you have type 2 diabetes, the odds are you are taking the prescription medicine metformin to help manage it. Also known by the brand names Glucophage, Carbophage, Riomet, Fortamet, Gluformin and Diaformin, among others, metformin is believed to be the world’s most prescribed antidiabetic...

www.phlabs.com