Let us know how it goes. I am in a similar situation.
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One thing I would say on HbA1c is apart from the fact that it metabolises in the sample it is skewed towards more recent glucose levels rather than going for an average over 30 days. I see that from my weekly blood tests and less frequently than every 6 weeks rapamycin dosing. My last HbA1c went up from 29.62 to 36.72 (mmol/mol). The blood draw was on Monday at 11 and I took Rapamycin the prior Friday at 7.30am. The previous results starting with the earliest were: 31.48, 32.68, 31.15, 34.97, 30.82, 31.8, 31.04, 33.01, 27.76 (then 29.62, 36.72).
The glycation of haemoglobin is in a limited extent labile, but I expect the drop over the next 5+ weeks to be quite gradual. The value of HbA1c varies a bit anyway.
This is a converter:
27.76 is 4.7% and 36.72 is 5.5%.
I did another blood draw yesterday and will get the results in the next few days.
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It depends. For me the issue is hepatic gluconeogenesis and an SGLT2i does nothing for that. The liver just makes more glucose to offset what is lost in urine. I take Empagliflozin 25 mg. The urine strips show plenty of glucose and sadly my FBG didnât change at all. Not a single mg/dl.
On the other hand Imeglimin reduces hepatic gluconeogenesis and that reduced my FBG from 100 ~ 110 to around 90.
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I have posted papers to the effect that in users of SGLT2i, neoglucogenesis partially compensates for the loss of glucose in urine.
Of course, there are still benefits of these drugs outside of losing glucose in urine.
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While itâs true that non-human primates (NHPs) are much closer to humans than mice, we still cannot use NHP studies to override human RCTs. A classic and painful example of this is the drug NXY-059.
In preclinical trials, NXY-059 showed amazing success in macaques (monkeys) for stroke treatment. It reduced brain damage by up to 50% and significantly recovered the monkeysâ motor skills. The monkey data looked perfect.
However, when it moved to a large human RCT (the SAINT-II trial with over 3,000 patients), NXY-059 showed zero benefit in humans compared to the placebo. The project failed completely, costing hundreds of millions of dollars.
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Furthermore, the most exciting part of that 2024 macaque study was the reduction in biological age. However, multiple human RCTs contradict this in non-diabetic people.
For example, trials like:
All of these human RCTs found that metformin has no effect on the epigenetic clocks (biological age) of non-diabetic people.
Although studies on non-diabetic humans are limited, after reviewing all the papers, the data points to a clear conclusion:
- Diabetic Patients: Metformin works well for them because diabetes accelerates aging. Metformin simply brings their accelerated aging back closer to a normal rate.
- Non-Diabetic People: The situation is much more complex. Different health conditions show different results. Crucially, current evidence suggests that for relatively healthy people, metformin might actually be harmful or disadvantageous.
This is why we cannot rely on the 2024 monkey paper to assume metformin will reverse aging in healthy humans.
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OK. Looks like weâve got a dog with a bone hereâŠjust wonât give it up.
âwe still cannot use NHP studies to override human RCTsâ I never suggested that. I did suggest that the anti-aging effects noted in the macaque trial were clear and unambiguous and we donât have a comparable human RCT.
I donât consider a RCT using HIV patients as comparable for obvious reasons.
As the macaque study showed, the effects of metformin go far beyond that of glucose control.
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Personally I am not a fan of metformin. However, people should be able to discuss scientific issues without being insulting.
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I seem to recall an old sayingâŠsomething like âif the other person resorts to insults; youâve already won the argumentâ.
I rest my case, Your Honour.
I think the argument against Metformin is quite strongly developed. However, there are many many molecules and now I have a theory of ageing which enables me to work out which interventions are likely to be synergistic and which are likely to be antagonistic I am not interested in trying out random molecules that may have an effect somewhere.
If you wish to take metformin then that is up to you.
Yes. Please refrain from insults. This is a friendly forum where we can disagree but where science should be the focus of discussion.
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So a question in search of a âTLDRâ answer here: what were the findings in your review in regards to detrimental effects from metformin on exercise, and implied or suggested mechanisms for such?
Thanks in advance
Here are some article on detrimental effects of metformin on exercise
The purpose of this study was to test the hypothesis that metformin diminishes the improvement in insulin sensitivity and cardiorespiratory fitness after aerobic exercise training (AET) by inhibiting skeletal muscle mitochondrial respiration and protein synthesis in older adults (62 ± 1 years)
In the metformin group, there was no overall change in wholeâbody insulin sensitivity after AET due to positive and negative responders. Metformin also abrogated the exerciseâmediated increase in skeletal muscle mitochondrial respiration.
Conclusion: Met blunts exercise training-mediated increases in vascular insulin sensitivity at the levels of conduit arteries and capillaries, in parallel with altered inflammation and glycemic benefits.
https://onlinelibrary.wiley.com/doi/10.1111/acel.13039
Although responses to PRT varied, placebo gained more lean body mass (p = .003) and thigh muscle mass (p < .001) than metformin. CT scan showed that increases in thigh muscle area (p = .005) and density (p = .020) were greater in placebo versus metformin
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