Canagliflozin vs Acarbose/Metformin for Anti-ageing

Hi everyone,

I’m looking for an alternative to Metformin for anti-ageing. I tried Metformin but I have a bad reaction to it.

As I understand it, a couple of alternative are Canagliflozin and Acarbose.

I tend to have high fasting blood sugar in the morning, nothing too outrageous and my HBA1c is in an acceptable range.

1 hour and 2 hour Post prandials are always very good.

Since I’m female, is it worth considering Canagliflozin? The data I’ve read suggests it only worked for male mice.

Acarbose tends to be good for post prandial spikes which I have no problem with, at this stage.

Any advice is greatly appreciated

thanks

For anti-aging it seems that acarbose is the best option for you given the ITP study results. The studies with canagliflozin did not, as you mentioned, show any benefit for females in terms of life extension.

The key issue with acarbose are the Gasto Intestinal issues it can cause - which seems to be primarily linked to wheat-based food, so depending on your diet, it might make sense. I encourage you to watch the latest Richard Miller podcast where he talks about this:

@RapAdmin thank you - I did watch the video, I got the impression that Acarbose was not effective for female mice either? Maybe I misinterpreted?

I don’t eat much wheat, but I have to say I’m a little concerned that Acarbose may affect the gut microbiome in a negative way.

If that was the case it may appear to be counterproductive to take it.

On a related question, thoughts on Acarbose vs FARXIGA?

C

No - Acarbose works for females:

There have been three major acarbose lifespan studies that all showed significant life extension results, with up to 17% seen in males at the highest dose. Life extension effects were slightly lower for females (Details here).

I’ve actually read that acarbose seems to be good for the gut microbiome… not sure where I saw it, but will search for the reference.

Ah - here it is:

Results

… At genera level, five flourished after treatment with acarbose, including Lactobacillus and Dialister, while Butyricicoccus, Phascolarctobacterium, and Ruminococcus were inhibited.

Conclusion

This study suggests that the benefits of acarbose for T2DM may correlate with the selective modulation of the gut microbiota.

Source:

and another:

By inhibiting host digestion, acarbose increases the flux of starch to the lower digestive system, resulting in changes to the gut microbiota and their fermentation products. Given the documented health benefits of short-chain fatty acids (SCFAs), the dominant products of starch fermentation by gut bacteria, this secondary effect of acarbose could contribute to increased longevity in mice. To explore this hypothesis, we compared the fecal microbiome of mice treated with acarbose to control mice at three independent study sites.

Conclusion

We observed a correlation between fecal SCFAs and lifespan in mice, suggesting a role of the gut microbiota in the longevity-enhancing properties of acarbose.

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Farxiga is depagliflozin (non-branded drug name), which is an SGLT2 inhibitor - same as canagliflozin. So - it “should” work pretty much the same as canagliflozin, (though without the actual trials we can not be 100% confident in this - but perhaps 95% confident(?).

Thanks RapAdmin. My PCP is bullish on Farxiga but not as big a fan on Acarbose.

Yes, absolutely - I think SGLT2 inhibitors are looking very promising. They seem to have a lot of benefits above the blood spike lowering… but I have increasingly found that acarbose is not too bad (for me, and my GI tract) as long as I avoid wheat based products… so currently I mix and match both SGLT2 inhibitors and acarbose (as well as rapamycin) and things are going well.

I used to get horrible gas with acarbose, but that is much less of a problem now.

Canagfliflozin´s application in humans

In addition to its glucose-lowering action, canagliflozin has been linked to a 31% decrease in heart failure hospitalization and cardiovascular mortality in diabetes patients. In another study, empagliflozine, also an SGLT2 inhibitor, was shown to increase life expectancy in diabetes patients. Due to those enviable qualities, canagliflozin and other SLGT2 inhibitors (empagliflozin, ertugliflozin, dagagliflozin) are widely prescribed to diabetes patients and sold by several big pharma companies such as Pfizer and AstraZeneca, bringing in roughly $7 billion in annual sales.

From the most promising longevity drug article.

Thank you @RapAdmin

Any thoughts on recommended dosage for Acarbose?

Should it me taken every day?

Acarbose comes in 25mg, 50mg and 100mg doses. The package recommendations are that you take it with the first bite of each meal (so yes, every meal of every day). I started at 25mg for a week, then moved to 50mg for a week, then 100mg with each meal. Now I am primarily taking an SGLT2 inhibitor, and occasionally dose 100mg with meals.

To get the best results I’ve seen that people chew the acarbose tablets to break it up. That works fine for me.

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@RapAdmin thank you!

So, would it be fair to say that:

Even though I have no problems with post prandial spikes, and Acarbose appears to have no effect on fasting blood glucose (which is a problem for me), taking Acarbose could still potentially be a good addition for its anti-aging properties?

Also, are there any SGLT2 inhibitors that are effective for anti-aging in women?

Ah yes - exactly as you describe.

The issue with post-prandial blood glucose spikes seems to be a universal problem - the more and higher they are, the faster you age. The current theory is that this is why SGLT-2 inhibitors and acarbose work to improve lifespan… so even though you think you have no problem with them, the belief is the lower they are, the better it is…

Fasting glucose is another issue entirely - and I suggest it would be beneficial to research ways of lowering that… I had a bit of this, fasting blood glucose around 100 a few years ago, which is higher than I wanted, but between more exercise, rapamycin, and SGLT2 inhibitors - I find my fasting glucose is now typically in the low 90s (USA measures, I think you’re in Europe so different there).

And - as far as we know, from the NIA ITP studies which only tested canagliflozin - it didn’t work for lifespan increase in females, and no other STLT2 inhibitors have been tested in that program. At the same time, there do seem to be a lot of benefits coming out on SGLT2 inhibitors - so there may be other benefits to taking them… but these benefits have not been confirmed in healthy people clinical studies.

Oh - and by the way - I think you might learn more about acarbose and canagliflozin in this podcast:

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That is great @RapAdmin

I will look at that. It’s such a shame canagliflozin isn’t an option for me. I exercise every day and it doesn’t seem to matter what diet I follow, it’s always 100 or so in the mornings. Usually goes back to <100 by lunch time.

I think sleep and hormonal fluctuations has a lot to do with it. Ever since menopause I occasionally wake in the middle of the night for an hour or so. I still wake up refreshed and never tired during the day, but I think if I didn’t have those times of awakening things may be different.

I’d really love to lower my fasting blood sugar. I’m starting my first dose of Rapamycin next week, will start at 2mg and tread very carefully.

I’m hoping that will help.

I have been on this journey for the past 6 months and have lost 10 lbs without trying. I started out with Canagliflozin 300 mg., and it worked great, but increased urination because instead of filtered glucose going back into blood stream from kidneys it goes through your ureter to bladder. But my HbA1c went down .75 which is a lot to 5.10. I tried 150 mg cutting in half because it is expensive. 84 euros for 30 tabs. The 150 did not work as well. Also, was taking Acarbose 100 mg right before meal with carbs, also worked well, I continued to lose weigh slowly, but steadly without dieting. But the gas was a problem, and then I read that Beano will not stop gas completely, but it stopped mine by about 50-75%. That problem solved. I now have switched to Empagliflozin 25 mg. and it works as well as 300 mg Canagliflozin, and cheaper also. Continue to take Metformin. If you are serious about losing weight, and reducing inflammation in your body, I would take all 3. Metformin inhibits glucose production in liver, SGLT2 inhibitors reduce in kidneys, and Acarbose blunts glucose spikes in the gut after a carb rich meal, especially if you are a type 2 diabetic. All 3 have different mechanisms of action in the body. Hope this helps everyone on my journey to low glucose and weight reduction. I personally have only had side effect listed

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My fasting glucose has been high ever since I tried a ketogenic diet. I am no longer on a ketogenic diet, but now I take rapamycin and still continue to be on a time-restricted eating regimen. Any one of these things may cause an increase in fasting glucose levels. That is why I think HbA1c is a better indicator of healthy glucose levels.

I hope Dr. Mikhail V. Blagosklonny is right. My fasting glucose is 105 to 115 mg/dL, I measure it at least once daily ~2 hrs after I get up. my fasting HbA1c levels have been okay. Strangely my last COMPREHENSIVE METABOLIC PANEL test at Quest just a few weeks ago indicated that my fasting glucose was 96 mg/dL.
Well, I’m just too old to worry about it. (LOL)

Fasting and rapamycin: diabetes versus benevolent glucose intolerance
“Puzzlingly, rapamycin can induce insulin sensitivity, but may also induce insulin resistance or glucose intolerance without insulin resistance. This mirrors the effect of fasting and very low calorie diets, which improve insulin sensitivity and reverse type 2 diabetes, but also can cause a form of glucose intolerance known as benevolent pseudo-diabetes”
https://www.nature.com/articles/s41419-019-1822-8

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@desertshores , yes my fasting BC tends to be between 105 to 115 as well, but my last hba1c was 5.2% or 33 mmol/l.

Next blood test I’m going to measure fasting insulin as well.