#41

Describing a multi-function drug as dirty just doesn’t make sense. Many vitamins and other supplements are multi-function. Why call them dirty? Here is another example of the “dirty” drug metformin’s multi-function:

“Rapamycin/metformin co-treatment normalizes insulin sensitivity and reduces complications of metabolic syndrome in type 2 diabetic mice”
“Here, we show that combination treatment with metformin ameliorates negative effects of rapamycin while maintaining its benefits”
https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13666

IMO: This is an important article to read fully for those taking rapamycin. It addresses the increased lipids and increased blood glucose levels in some subjects taking rapamycin.

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#42

That is a great article. It’s too bad that many people don’t read these articles fully.

#43

Is there a mention of the proper dosage of Metformin per mg of Rapamycin?

#44

He just says that because it has multiple effects on the body and pathways. Matt K would say the same about fasting. One of the things he likes about rapamycin is that it only affects MTor. I can see how that would appeal to a scientist who has to worry about confounding factors. I am happy to take a “dirty” drug!

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#45

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David Weinkove


@dweinkove

The power of combinatorial approaches in aging. ⁦

@mkaeberlein

⁩ shows how some drugs can synergize with metformin to increase lifespan in C. elegans. Proof of concept for his spin out ⁦

@OraBiomedical

⁩ #ARDD2022

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#46

Latest argument against metformin dosing for non diabetics. I tend to agree. However since Rapamycin creates Rapamycin diabetes and based on the ITP data, I will still take metformin before switching to acarbose when I run out of metformin.

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#47

This in from Dr. Peter Attia - a surgeon I respect. “A Recent Metformin Study Casts Doubts on Longevity Indications”.

I will stick with my Acarbose 50 mg first bite of a meal.

Link: A recent metformin study casts doubts on longevity indications

Let’s hope the TAME trial with Metformin can give us some definitive answers.

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#48

Yes, as time goes by, metformin seems less and less appealing. Acarbose appears to be a better alternative. I still think it’s good for diabetics and pre-diabetics though.

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#49

Direct evidence that metformin alters lipids to provide cardioprotection, independent of type 2 diabetes control http://tinyurl.com/3artyrjm

It helps attenuate the lipid issues that Rapamycin causes.

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#50

Question to Metformin users, advocates, prescribers: are any of you using Rapamycin in overweight, minimally motivated, pre-diabetics already on Metformin? I am a little worried about overdoing mTOR inhibition in a non-exercising person…??

Thanks for any thoughts.

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#51

This study somewhat reassuring: the combo seems to protect muscles in culture, but … what about in living humans?

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#52

The long term effects of metformin over 20 years:

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#53

So, to summarize:

Metformin provided greater longevity to diabetics than the control in the first 3 years only. After 5 years on metformin, their diabetes progressed to the point where it was more debilitating than the metformin could overcome and they had shorter lifespans than control.

Moral of the story: Don’t get diabetes.

The study did not look at non-diabetics taking Metformin unless I missed it.

While metformin does appear to confer benefits to longevity in the short term, these initial benefits are outweighed by the effects of type 2 diabetes when patients are observed over a period of up to twenty years. Longer study periods are therefore recommended for studying longevity and healthy lifespan.

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#54

I have been taking metformin for decades with a brief stoppage to see if it improved any of my biomarkers or if I felt better not taking metformin. Stopping metformin had no noticeable effect, but I only stopped it for a few months.

If you do a Google Scholar search for "Metformin and sarcopenia’ you find a multitude of articles suggesting that metformin mitigates or stops the progression of sarcopenia.

“Participants who took metformin alone or combined with other drugs exhibited a lower risk for sarcopenia than those who took no medication”

“The four cuproptosis-related genes PDHA1, DLAT, PDHB and NDUFC1 may be the diagnostic biomarkers for sarcopenia, and metformin holds great potential to be developed as a therapy for sarcopenia.”

On another thread I posted a picture of myself at 81 yrs old. While I am not a body builder you can see I have more than sufficient muscles for my age. My ability to avoid any significant sarcopenia so far I attribute to exercise and metformin.

Due to the many benefits and few downsides of taking metformin for the synergistic effect with rapamycin and prevention of sarcopenia I would certainly recommend it to anyone getting on in years.

Identification of the cuproptosis-related hub genes and therapeutic agents for sarcopenia - PubMed.

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#55

Metformin may reduce dementia risk through neuroprotection not mitigation of diabetes

Dementia is a largely untreatable syndrome that is epidemiologically associated with metabolic diseases such as type 2 diabetes (T2D) and obesity. Drugs used to treat T2D such as metformin are inexpensive, safely given to millions of people, and have also been reported to slow neurodegeneration. We hypothesised that the neuroprotective benefits of metformin might extend to metabolically healthy individuals and tested this hypothesis in a mouse prion model that recapitulates key common features of human neurodegenerative disease, including synaptic loss and motor impairment. These features and the time course of this model (24 weeks) allows the effects of metabolic risk factors and metformin to be tested and potentially generalised to other forms of neurodegenerative disease. Mice fed a high fat diet (HFD) developed high adiposity with impaired glucose and insulin homeostasis, similar to the effects of chronic obesity seen in humans whereas mice on matched control diet (CD) remain metabolically healthy. Chronic treatment with metformin in HFD-fed mice significantly increased survival and health span relative to vehicle-treated mice. Mice fed a HFD also had a modestly extended health span relative to mice fed CD, as measured by development of motor signs of prion disease. Metformin also significantly extended health span in metabolically healthy CD-fed mice. Using targeted mass spectrometry, we found that metformin reached deep brain structures at likely functional concentrations, raising the intriguing possibility that it may exert its neuroprotective effects directly on the brain. Together, these data broadly support the premise of repurposing metformin for neuroprotection, even in metabolically healthy individuals.

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#56

I’m taking it. Read a shitload and the evidence seemed to be for it upon the whole. Told my new family physician and she was a bit disturbed about my taking rapamycin off label from what admittedly little she knew of it.

But when it came to Metformin, she said every cardiologist she knew was taking metformin on the down low because it’s such an all around great drug with well documented cardio protective properties.

The only real downside to metformin that I could tell is it impairs vit B12 absorption so need to crank up supplementation.

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#57

Statistically, people who are on metformin for diabetes = have a 17% of lower all-cause mortality, compared to people who are healthy and not on metformin >> that’s a pretty strong incentive for taking it. I am mindful of the fact that Peter Attia has stopped taking it. He is a very through guy.

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#58

I understood Attia stopped Metformin due to higher blood lactate which interfered with his efforts to raise his “zone 2” threshold (<2 mmol/L). Somehow Metformin interferes with mitochondrial function to make exercise feel harder (burning glucose without oxygen vs fat with oxygen). I felt this effect myself. I’m not sure how this effect is related to the reported decrease in adaptation from exercise while taking metformin.

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#59

If not Metformin, what then will help reducing glucose spike after taking rapamycin? Acarbose? I take 500 mg Metformin with Rapamycin. My Vo2Max is 30 (per Apple Watch it’s high, probably high for my age category).

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#60

For people takin metformin, what is your schedule. When is best to take metformin? In the morning, during the day? Before bed?

I have a pack of metformin I said I will try. I am healthy, low BS and insulin. I exercise every day in the morning, but usually eat my last meal around 8-9 PM. My fist meal of the day is usally late breakfast around noon or ealy lunch around 1-2PM.

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