I think calling this a “study” is overly generous. I read it, and nothing seemed vaguely informative.
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Confused about Conclusion: if you are NOT diabetic or (if you are not) taking rapamycin… or did you want to say “if you are not diabetic but taking rapamycin”.
Which one did you mean?
Sorry. Let me clarify.
If you take rapamycin, you can take metformin due to the Rapamycin diabetic effect.
If you are diabetic you can take metformin.
Other than that, you shouldn’t. At least according to that report.
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Another reason not to take Metformin:
Thank you. I’m not diabetic and I take rapamycin. Started taking low dose (250 mg/day) Metformin. Had my first BG test done yesterday (after 1 month on Metformin). It did not lower glucose for me. Previous BG was 92 and yesterday it was 98. Could be because dose is too low or because I had a cup of coffee (black) just before the test. Next time will try without coffee.
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The dose is too low. May need to take at least 500 mg twice a day.
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First, glad to see you back. I enjoy arguing with you.
From the article you cite, it looks more like association than causation.
“In men, there is strong evidence that low testosterone levels are significantly associated with T2DM”
From the same study you cite as a reason not to take metformin:
“Metformin may also inhibit the growth of cancer cells. The mechanisms underlying this protective effect are not well understood and may involve the activation of multiple pathways [2,42]. The cell cycle arrest in metformin-treated breast cancer cells seems to involve the activation of AMPK and down-regulation of cyclin D1, and requires p27Kip1 or p21Cip1 [44,45]. Metformin was reported to suppress HER2 (ERBB2) oncoprotein overexpression through inhibition of the mTOR effector p70S6K1(RPS6KB1) in human breast carcinoma cells [46].:”
Plus in the end, the article gives a plug for metformin:
“metformin is still widely accepted as the first-line therapy because of its low incidence of microvascular and macrovascular events and its beneficial effects on plasma lipids and body weight” (bold type is mine)
The fact is that the huge number of studies showing the benefit of metformin far outweigh the negative studies. Are you saying that these medical experts are all wrong and that suddenly a few negative studies are right?
“At this time, there are more studies showing the benefits of metformin than the negative effects of metformin. According to a review of 8,000 studies published in the journal Diabetes Care, there were 4,108 studies showing the benefits of metformin and only 617 studies showing the negative effects of metformin.”
This figure was obtained from OpenAi.
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It was retrospective so it couldn’t be blinded. It’s not an RCT - there’s not a single RCT tah I know of for longevity in humans for any drug where the end point is death.
But the metormin study is pretty good given that it’s retrospective only. The size of it and the quality of the matching were both strong. Metformin isn’t given to the healthiest diabetics in the UK - and there’s no explanation why metormin patients outlived non-diabetics beyond the impact of the drug.
I suspect a reasonable approach would be to use metformin to target a lower Hba1C than is the diagnostic cut off for diabetes. It is - after all a fairly arbitrary cut off point
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And yet it can’t be repeated
I think this would also be a reason not to take rapamycin.
Of course it can, just with a different cohort
Since it is a retrospective study, they removed anyone taking Metformin + another diabetic drug from the Metformin group. This is key because it only includes the healthiest diabetics. If someone’s diabetes got worse, and they needed Metformin + another treatment, they were dropped from the Metformin group. When those people were added back in, there was no change in lifespan. See the study I posted above. Same cohort - different results. It’s all in how you manipulate the data. To me, there is no reason to take Metformin unless you are diabetic or taking rapamycin. If you are healthy and exercising, you don’t need it.
I am taking up to 1 g of Metformin daily. Higher doses coincide with the Rapamycin dose. On the last two days before my Rapamycin dose, I don’t take Metformin. I take 1 g of Metformin the night before my Rapamycin dose as it also disables the CPY enzyme similar to GFJ.
I do love the fact that Metformin works synergistically with Rapamycin to blunt Rapa’s bad effects and enhance its good ones. Also, the combination knocks out fatty liver development which 25% of Americans suffer from!
Another study which shows Metformin is great for diabetics (DM).
A diabetic who needs only one diabetic drug is surely no healthier than a non-diabetic who only needs zero diabetic drugs?
Or have I misunderstood?
And my understanding was that the other diabetic group was also only taking one diabetes drug
A diabetic is more unhealthy than a non diabetic regardless of drug.
I think Nir needs to stop slogging a dead horse.
Yes, i had another look at the original study and it seems they treated the Metformin and sulphonylurea groups exactly the same. So any “survival ratchet affect” would apply equally.
Similarly with the control non-diabetic group, they excluded anyone who needed an additional (ie first) diabetic drug
In your view
In many others view he should continue.
Completing the TAME study would be of tremendous value to the “longevity / anti- ageing field”
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Null results are certainly helpful but I believe time and money would be better spent on drugs that actually work in model organisms.
And if rapamycin pushes blood sugars outside the healthy range then reduce the dose / frequency, don’t fall into polypharmacy.
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