#21

I really apreciate how you push back against the cult of statistical significance, it becomes even less relevant for N=1 studies (which will become more important with time). Stat sig will be replaced by… something else (and AI will help)

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#22

I struggle to think anything less than 15% is meaningful.

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#23

What do you think about canagliflozin then, afaik 14% increase in median survival for male mice only?

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#24

How long you have been on the combo and what positives have you noticed?

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#25

I agree. Haven’t read the paper yet, but this seems very promising. Non-human primate data published in Cell def should be considered in a very serious way and stacks up quite high from a hierarchy of evidence perspective even again mouse ITP.

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#26

I’d love to learn more about if that is the case!

Also of note is that the medical team of Bryan Johnson do have it as a key pillar of his regime:

Upon waking:

  • Metformin ER 1,500 mg (Rx)

At last meal:

  • Metformin ER 500 mg (Rx)
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#27

But you can also look at the effect in ITP when Met was combined with rapa which increases the signal that something is happening with Met

(And for humans on a 7 or 14 day Rapa cycle Met might also help with the potential nTORC1 rebound effect from Rapa as discussed elsewhere on the forum).

For me it’s also about that if Met is good for:

  • brain aging
  • cancer

Those are the two things we have least control over vs the other main longevity and healthspan killers (pun intended): cardiovascular disease, osteoporosis, sarcopenia, metabolic disease can we controlled to a very high agent with todays tools if one works hard at it (early enough)

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#28

I honestly don’t know. It seems like when it comes to worms, flies, and sometimes mice, anything that stresses them makes them live a little longer. We see so many studies that show small increases. How many of these will apply to humans?

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#29

@KarlT Yes. It is all so hard to predict. I have settled on the idea that metformin stresses the body in a way similar to exercise. So that’s good for people who don’t actually exercise. For people who do exercise enough, I don’t think metformin is useful due to issues with lactate, MPS, etc. I take it only around rapa (3 days/ 14 days) when I’m not exercising vigorously. Maybe that’s wrong.

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#30

@约瑟夫_拉维尔
I was also not taking Metformin because of its potential effects on exercise but that paper makes me want to try it. The effects on mitochondria in much more complex and nuanced than initially thought and in the end it seems to be positive and beneficial. Probably Attia over reacted to the early findings.
Also the pharmacokinetics is pretty simple and rather fast so, when taking 500mg in the morning after exercise, there is mostly no Metformin left on the next morning and it should not impair the training session.
I will try that. (Metformin after morning training)

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[Edit] This is more complex and nuanced than that in fact. Here is an updated post: What's the Deal with Renewed Interest in Metformin? - #55 by cl-user

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#31

@cl-user Attia was probably using a lot. That would be like him to maximize something he believed in. Originally, 5-ish years ago, when I had trouble exercising (zone 4-5, endurance) i was taking a low, non-extended release Metformin dose about 2 hours before exercise…so right in the peak (thanks for the chart). More recently on an extended release (and a statin) I just didn’t feel right when I was taking it day after day. And when i experimented with stopping the metformin i felt better. Now that I no longer take the statin (another experiment that paid off), perhaps there is room for metformin again if I need it. The akkermansia is keeping my hba1c low so I’m not in a rush. For now, I just aim for the Rapa + Metformin compounding effect. Good luck with the Metformin.

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#32

Metformin promotes hormesis, what does not kill us makes us stronger

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#33

New study on Metformin Slow Brain Aging in Monkey Sept 2024 Nature:

https://www.nature.com/articles/d41586-024-02938-w?utm_medium=Social&utm_campaign=nature&utm_source=Twitter#Echobox=1726156992

Screenshot 2024-09-13 at 2.33.11 PM
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Anti-Aging Enthusiasts Are Taking a Pill to Extend Their Lives. Will It Work? (NY Times)
#34

Thanks. This is a news story about the paper that was in Cell

Interesting that:

In the meantime, Liu and his colleagues [have launched a 120-person trial](ClinicalTrials.gov) in collaboration with the biopharmaceutical company Merck in Darmstadt, Germany, which developed and manufactures metformin, to test whether the drug delays ageing in humans.

That will report out in 2026, so while much smaller than TAME, might have data sooner

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#35

That looks like an excellent clinical trial. I hope it has positive results!

#36

They use 1,000 mg/day of Metformin hydrochloride extended-release tablets in this trial. So 2x the HED of what they tried in monkeys?! Metformin decelerates aging clock in male monkeys - #15 by adssx

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#37

The Chinese paper results seem fairly clear. I’m not going to criticise it simply on the basis that “it’s Chinese and therefore inherently untrustworthy.”

Metformin is a drug that has shown longevity effects in worms, flies and to some extent in mice but only circumstantial evidence in humans. These primate results go some way towards filling that gap in knowledge.

As far as effects on muscle strength goes, I can only state my own experience. I’m a 67 y-o male. I exercise on alternate days. 500mg SR metformin before breakfast. I don’t do much in the summer; just some jogging and pull-ups on a high bar. I can do 18 pull-ups (maybe more if I really tried) which, according to an athletic performance comparison website I found, puts me in the top 1% for my age.
That’s good enough for me.

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#38

FWIW…

As I have posted countless time.

“If you wait until you are ready, it is almost certainly too late.” ~Seth Godin

“Keep waiting, the time you wait you will never get back.” ~Joseph

In my view another no brainier.

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#39

I get hypos on metformin (500mg IR), perhaps if there were 100/200mg tabs, I could take it.

My average dose of Rapamycin has been 2mg/bi-weekly for 1.5 years.

Could I make the assumption that I still have very high insulin sensitivity?

#40

Have you tried cutting 500 mg IR half? (I assume you cannot cut half the SR/XR version)

I like idea of GMRx4: single pill, ultra-low-dose combination of metformin XR 350 mg + dapagliflozin 2.5 mg + sitagliptin 17.5 mg. Not yet commercialized: Developing Late-Stage Drugs - Our Pipeline - George Medicines

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