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What is metformin's secret sauce?

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Re: What is metformin's secret sauce?

#11

Post by Alex3917 »

> metformin blocks a specific part of the cell's energy-making machinery called mitochondrial complex

Keep in mind that any mitochondrial complex I inhibitor that is sufficiently strong is going to cause PSP if you take it for long enough, which is basically a fatal and untreatable version of Parkinson's disease. I haven't seen much research on this being a risk specifically for metformin, but I'd be careful about trying to use it prophylactically for longevity purposes rather than for a specific medical condition.

Re: What is metformin's secret sauce?

#12

Post by vlod »

justinko wrote: post #8
vlod wrote: post #2

FTA: "But until now, scientists have been unable to determine how, exactly, the drug works." Try that next time you submit a PR: Yeah... it works, but "I am unable to determine how exactly". I find this concept absolutely mind blowing. We take drugs that the creators of the drugs don't understand how they work. I realize that biology is hard to understand, but this sounds crazy.

Sorry bro, human biology is infinitely more complex than your CRUD app.

Oh... I agree.. I'm just shocked at the attitude.

i.e. "We don't quite know how it works... but statistically we think it will help, with these side-effects.. good luck"

Re: What is metformin's secret sauce?

#13

Post by aftbit »

vlod wrote: post #2

FTA: "But until now, scientists have been unable to determine how, exactly, the drug works." Try that next time you submit a PR: Yeah... it works, but "I am unable to determine how exactly". I find this concept absolutely mind blowing. We take drugs that the creators of the drugs don't understand how they work. I realize that biology is hard to understand, but this sounds crazy.

I've submitted just such PRs before, usually with a comment along the line of "this hack is dumb and I do not yet understand why it is necessary, but it works now, tests prove it works, and I have more urgent things to do." Sometimes this is unacceptable but often it is just what the doctor ordered.

Of course, unlike with biology, it is usually not beyond my skills to eventually understand the whole system, but it may be beyond my time availability. With biology, the whole thing is just too complex to grok.

Re: What is metformin's secret sauce?

#14

Post by inglor_cz »

vlod wrote: post #2

FTA: "But until now, scientists have been unable to determine how, exactly, the drug works." Try that next time you submit a PR: Yeah... it works, but "I am unable to determine how exactly". I find this concept absolutely mind blowing. We take drugs that the creators of the drugs don't understand how they work. I realize that biology is hard to understand, but this sounds crazy.

Biology is a result of billions of years of constant evolutionary struggle on a planetary scale, without rhyme or reason, very much not intelligently designed. Whatever random mutation worked, worked.

We the IT people love to complain about esoteric interplay of hardware, OS, apps and network. There is a lot more phenomena in constant interplay even in mere amoebas, not to speak of human bodies.

Not to mention that you just cannot put breakpoints into a living organism and read its current status on screen.

I find it positively crazy that we know something about biology at all. The intrinsic obstacles are just so much higher than in software.

Re: What is metformin's secret sauce?

#15

Post by aftbit »

vlod wrote: post #2

FTA: "But until now, scientists have been unable to determine how, exactly, the drug works." Try that next time you submit a PR: Yeah... it works, but "I am unable to determine how exactly". I find this concept absolutely mind blowing. We take drugs that the creators of the drugs don't understand how they work. I realize that biology is hard to understand, but this sounds crazy.

What's the alternative? Never develop or deliver a life-improving medication until we can fully understand it from first principles? Gonna be waiting a long time IMO.

Re: What is metformin's secret sauce?

#16

Post by MaxDPS »

lordnacho wrote: post #6
Trasmatta wrote: post #3

Earlier quoted context omitted.

That's very common actually! The mechanism of action for many drugs is unknown. And then it gets even weirder with psychoactive drugs: eventually the answer is "this drug effects this neurotransmitter which gives you this subjective first person experience, and we don't really know why". It brings up a lot of philosophical and existential questions!

How do people come to find these drugs then? If you don't have a theory about how something works, what would make you test whether it works?

Sometimes there is a theory, but it’s also possible for a drug to help in other (unrelated) ways as well.

Re: What is metformin's secret sauce?

#17

Post by pedalpete »

vlod wrote: post #2

FTA: "But until now, scientists have been unable to determine how, exactly, the drug works." Try that next time you submit a PR: Yeah... it works, but "I am unable to determine how exactly". I find this concept absolutely mind blowing. We take drugs that the creators of the drugs don't understand how they work. I realize that biology is hard to understand, but this sounds crazy.

It's the same with neurology. We pretend we understand how the brain works, but much of what we are understanding is our current conceptual knowledge, so it's theoretical.

We work with Phase-targeted auditory stimulation to enhance deep sleep (https://affectablesleep.com). We know we can stimulate the brain during sleep and measure the increase in electrical activity which is the result of increased synchronous firing of neurons, but the reason why we are able to create this result is just a theory. However, the behaviour itself is consistent, and replicated.

Re: What is metformin's secret sauce?

#18

Post by pitpatagain »

lordnacho wrote: post #6
Trasmatta wrote: post #3

Earlier quoted context omitted.

That's very common actually! The mechanism of action for many drugs is unknown. And then it gets even weirder with psychoactive drugs: eventually the answer is "this drug effects this neurotransmitter which gives you this subjective first person experience, and we don't really know why". It brings up a lot of philosophical and existential questions!

How do people come to find these drugs then? If you don't have a theory about how something works, what would make you test whether it works?

In the case of metformin, the direct line is from guanidine in french lilac being used since the middle ages for diabetes. Guanidine is effective, but long term liver toxic.

Once actual chemistry broke open our ability to analyze that drug, related chemicals could be synthesized and studied, which led to biguanidines, of which metformin is one, which were tested in animals.

Many drugs are found this way by looking at chemicals related to ones we already know about, and then testing on animals and humans. Self testing of new drugs by researchers used to be very common.

How did folk medicine come to know the effects of guanidine? Dunno.

Re: What is metformin's secret sauce?

#20

Post by klipklop »

Alex3917 wrote: post #11

> metformin blocks a specific part of the cell's energy-making machinery called mitochondrial complex Keep in mind that any mitochondrial complex I inhibitor that is sufficiently strong is going to cause PSP if you take it for long enough, which is basically a fatal and untreatable version of Parkinson's disease. I haven't seen much research on this being a risk specifically for metformin, but I'd be careful about tr…

Very interesting. I wonder if there is any study/evidence indicating PSP can happen to somebody taking metformin that does _not_ have T2D.
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