Acarbose, An mTORC2 Promoter We Should All Take?

I have it in my cupboard and I keep it in my wallet for when I may be eating more starch and I have not taken an SGLT2 inhibitor, but generally don’t like, acarbose.

Its gotten good results in terms of lifespan improvement from the NIA ITP studies, but the side effects of excessive gas, and sometimes diarrhea are so common as to make this medication less than desirable for me (your results may differ).

But I saw these recent comments to renew my interest in acarbose. Perhaps it might be optimal to take lower doses of acarbose, even if you are already taking SGLT2 inhibitors…

Research has shown that higher mTORC2 activation seems to increase lifespan and healthspan:

Additionally, it was noted that Acarbose can increase mTORC2 activity:

So, perhaps acarbose is something that should be added to our protocols even if we are already taking an SGLT2 inhibitor like canagliflozin or empagliflozin and blood sugar spikes are not an issue at all?

Your thoughts?

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Additional commentary:

My hunch is that the combination can be useful because:

a) acarbose works on starch that is consumed but SGLT-2 inhibitors also works with glucose/sucrose that is consumed

b) the combination in lower doses could be a good strategy to reduce side effects from taking too much of one type (UTI/fatigue for SGLT-2, and gastrointestinal issues for acarbose). They work via different mechanisms that don’t seem to interact as well.

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And another opinion from a doctor familiar with these compounds (and who takes rapamycin himself):

and another doctor weights in with diet info for a patient of his taking high doses rapamycin, and also 300mg of acarbose:

Dr. Mert Ergol, also had this to say about SGLT2 Inhibitors for anti-aging:

My philosophy with these agents is not to be married to them but rather to date them–take them intermittently for months at a time, cycle them. There is still so much uncertainty about what they do. Metformin in particular depletes b12 over time, there is a rationale for giving yourself time to re-equilibrate.

Also, I like the idea of taking the sglt2i at night to deplete body glucose, accentuate the overnight fast, declutter the mitochondria, induce starvation autophagy.

Metformin induces secretion of glp1 which works at the brain to control appetite. https://pubmed.ncbi.nlm.nih.gov/30518693/

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Given the long half-life of sglt2i, I wonder if it makes a big difference whether one takes it in the morning or night. My strategy has been to consume it an hour or so prior to my first carb-y or sugar meal of the day (when I’m not on keto). I take 25mg empagliflozin, and assume that a bunch of it will be sticking around during the night and even the day after.

Also isn’t sglt2i only supposed to attenuate higher sugar levels? If one’s sugar levels have stabilized after dinner, how much difference would sglt2i at before sleep really make?

Yes - good questions. I’m not sure of the answers - I was just posting one doctor’s opinions.

I usually take my empagliflozin just like you - an hour before any meal, in the morning (but typically just eat lunch and dinner). I think you want the peak, or higher blood levels during the time of the day you’re eating your main meals… but I’m not sure what the effect would be if I took it at night. Something to test when I have my CGM on - to see the difference.

Here is the blood level curve below:

41598_2017_2895_Fig6_HTML

Yes - the SGLT2i drugs lower peak blood glucose levels. After reading that doctor’s comments I’m going to try at some point dosing at night and seeing what impact it has on fasting blood glucose levels in the morning. An interesting experiment.

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I’d be very interested to see your results! For the usecase of consuming at night , I also wonder if metformin/berberine would be a better option (ignoring effects on exercise here, or assuming one’s being sedentary around the days of ingestion). Metformin would be explicitly reducing the amount of gluconeogenesis but sglt2i will only prevent reabsorption of any high levels of sugar in the kidney.

did you ever do this experiment for yourself?
also found this interesting in regards to when taking the dose