A diabetic taking only Metformin is healthier than a diabetic who needs metformin plus another medication as Metformin is the first line of defense. When the diabetes disease progresses and the diabetic is in worse shape, doctors add more drugs. If the doctors add more drugs as the patients health deteriorates, they are removed from the metformin study as they don’t want patients with polypharmacy.
It’s like doing a longevity study and removing people from the study when they develop a disease like cancer, CVD, diabetes, etc … I guarantee the group that is left will live very long lives as you have removed everyone who develops worse health. It skews the results when you do that. No wonder diabetics on metformin lived longer than non diabetics!
“A diabetic taking only Metformin is healthier than a diabetic who needs metformin plus another medication as Metformin is the first line of defense.”
Yes, but a diabetic taking only Sulphonylurea is also healthier than a diabetic who needs Sulphonylurea plus another medication. The two groups were treated identically.
Also the control group of non-diabetics excluded anyone who needed to start a new diabetic medication. So they too were treated identically
Your other big assumption is that metformin was the sole first drug in the treatment protocol and that Sulphonylurea was only used for difficult or more severe cases. During the period in question - metformin and Sulphonylurea were both used as a first line treatment. It’s only recently (mainly because the outcomes for metformin are much better) that metformin is used as first line to the exclusion of Sulphonylurea
I think we’re probably quite close to agreeing on lots of this. I totally accept that there’s no hard evidence to take metformin for increased lifespan. But…
Do you agree that diabetics given metformin who don’t go on to need additional diabetes drugs to control their diabetes live longer than non-diabetics who don’t go on to need additional diabetics drugs?
In which case - I suggest it would follow that either:
metformin is adding to longevity through some non-diabetes related mechanism (in which case why wouldn;t it work in non-diabetics?)
metformin is adding to longevity through some diabetes-related mechanism such as lower blood sugar or diabetes-induced-inflammation which improves their health to such an extent they live longer than the the non-diabetics. (In which case it suggests that non-diabetics’ health could be improved by the similar mechanism - especially if they are peri-diabetic)
There’s no magic to the level at which diabetes is diagnosed. And for someone with a high (but not clinically diabetes) HBa1C there is a reasonable but unproven case for low dose metformin as follows:
Here’s a proposed pragmatic approach: If you are pre-diabetic and have say, gum disease oir some other signs of chronic inflammation - then metformin is worth a trial because it might alleviate your gum disease/chronic inflammation and reduce your Hba1c.
The side effects from a short personal trial are very low and even if reducing inflammation and HBa1C doesn’t add to your lifespan it should increase healthspan.
Is that something you could agree with? I’m genuinely interested - not just seeking an argument
I have been taking 1000 MG of Metformin. I’m asking my doctor for permission to up it 1500 MG. My average glucose for the last 30 days has been 90 MG. 83% of the time I am within a 70-110 range. 10% above 110.
TAME is not purporting to test the drug with the greatest potential for longevity. Even Nir would admit that. It is testing a drug that is demonstrably safer in the eyes of the FDA. If it is successful, then it will pave the way for testing of other longevity drugs, including rapamycin.
The Sinclair and Rogan interview is the first longevity podcast I watched. It was interesting at the time. It’s a good watch for someone just getting into longevity.
Nice little clip and I would concur from my experience. My muscles are tighter, shredded - smaller compared to before rapamycin and metformin. But I have increased strength with smaller muscles. They still rock - just not OMG rock.
Also, I have had a great success switching from Metformin to Acarbose. Metformin made me gassy and gave me diarrhea. I had to space doses and really didn’t feel well.
I don’t seem to have these issues with my first few days of Acarbose. And, Acarbose is suppose to work better in longevity with rapamycin. Win - win! I hope to get up to 3 pills of Acarbose per day - maybe in a week or so. That could never happen with Metformin.
Thinking about changing to Acarbose, given the ITP data. Have been taking Metformin for a year now. I’ve been fortunate, in that I haven’t had any noticeable side effects. I do go pretty hard at the gym too - zero difference pre v post Metformin (I will caveat this by saying I’m def no elite athlete ).
Thanks for your insights Agetron
It’s starting to look like Acarbose is a good replacement for Metformin. Others have had the opposite experience though with Acarbose having more severe side effects. I guess it’s up to your own personal biochemistry? Either one is needed and you should pick the one that suits you best.
I have a different perspective on avoiding metformin that I’ve mentioned before to some extent.
The evidence for exercise for diabetes/diabetes prevention and healthspan/all cause mortality is overwhelming. The evidence for the metformin + exercise group showed interference here in about half vs controls:
Why give up a known benefit by taking metformin when there are other highly targeted ways to lower blood sugar?
Acarbose + rapamycin makes a lot more sense and I’ve mentioned this way back. Acarbose isn’t systemically absorbed and it’s not a “dirty” drug like metformin where there are so many offtargets. The main snag is “acarbose resistance” but I’ve detailed the solution before.
Metformin might work with rapamycin, but metformin-only ITP trials were a dud. We just don’t have good human data on healthy individuals in terms of all-cause mortality prevention and new data suggests null. All this considered, it doesn’t seem to make sense for me to take something that interferes with exercise, when we have acarbose that doesn’t.
Acarbose is first-line in several Asian countries btw - lipid profile improved as a secondary outcome in a fairly large MARCH2 trial showing acarbose noninferiority to treat T2D compared to metformin in terms of HbA1c. If we are trying to address elevated blood sugar/IR via AMPK as a risk factor - acarbose does this indirectly and doesn’t interfere with exercise. Since we are targeting AMPK (acarbose + exercise) + direct mTORi (rapamycin) as the general rationale for the combo - seems like acarbose+rapamycin+lifestyle factors make way more sense.
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