Canagliflozin - Another Top Anti-aging Drug

Yeah it’s unclear why in male mice there are much stronger effects than the smaller effects on females and very important to figure out the root causes if possible.

There are some clues, if you read up Miller’s ITP related research on 17aE2 where he suggested MEK1/ERK pathway

Recent article on SGLT2 inhibitors:

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I think I may have a UTI associated with my Canagliflozin use, some of the signs and symptoms are there including kidney (I think?) pain on my right side. I had amoxicillin on hand so I took one, I’ll go get checked if it doesn’t resolve soon. Can’t figure out what else it would be

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I have a supply of empagliflozin but have been hesitant to start taking it for this very reason. Perhaps I am being a little overly cautious

Hope whatever it is resolves soon.

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It could also be this

FDA Drug Safety Communication: FDA strengthens kidney warnings for diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) | FDA.

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Signs and symptoms of acute kidney injury may include decreased urine or swelling in the legs or feet.

That is a relatively old study. 101 patients with kidney problems are very low considering the number of people that are taking or have been taking canagliflozin, plus it was for both
canagliflozin or dapagliflozin.

I couldn’t actually find a number for the number of people prescribed canagliflozin but it is surely in the 10’s of thousands.

However, I did find a more recent (2019) article in the New England Journal of medicine that seems to refute that by saying: “In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years.”

https://www.nejm.org/doi/10.1056/NEJMoa1811744

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A new study on empagliflozin:

The SGLT2 inhibitor empagliflozin improves cardiac energy status via mitochondrial ATP production in diabetic mice

Empagliflozin, a sodium-glucose co-transporter 2 inhibitor developed, has been shown to reduce cardiovascular events in patients with type 2 diabetes and established cardiovascular disease. Several studies have suggested that empagliflozin improves the cardiac energy state which is a partial cause of its potency. However, the detailed mechanism remains unclear. To address this issue, we used a mouse model that enabled direct measurement of cytosolic and mitochondrial ATP levels. Empagliflozin treatment significantly increased cytosolic and mitochondrial ATP levels in the hearts of db/db mice. Empagliflozin also enhanced cardiac robustness by maintaining intracellular ATP levels and the recovery capacity in the infarcted area during ischemic-reperfusion. Our findings suggest that empagliflozin enters cardiac mitochondria and directly causes these effects by increasing mitochondrial ATP via inhibition of NHE1 and Nav1.5 or their common downstream sites. These cardioprotective effects may be involved in the beneficial effects on heart failure seen in clinical trials.

https://www.nature.com/articles/s42003-023-04663-y

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I started looking at these SGLT2 inhibitors and if you had a choice between Canagliflozin or Empagliflozin which would you choose? Are there mayor differences? I noticed Canagliflozin is available as a combination with Metformin. Would that be a good choice? What would be the dosage for longevity?
I read there is no high probability for hypoglycemia… has anyone experienced any trouble with low blood sugar?

Here was my experience with Canagliflozin and empaglflozin … I think it may be to some extent your body’s reaction to them. Canagliflozin is the drug that was used by the ITP, so it has more data on it in this application. But, they should both have similar results one would think. Do your research on them in terms of side effects and risks. I think I’ve heard that Empagliflozin has lower risk of UTIs, but I think for males its extremely low in either case. Canagliflozin for Anti-aging - One Month and 4 Month Updates

Dosage, I think most people are just taking the recommended dosing levels that go with the drugs. Its a good idea to track your blood glucose levels while starting these just to see how your body is responding. Either CGM or finger prick methods are fine for BG tracking.

I wouldn’t say there is “no probability” for hypoglycemia, but the risk seems relatively low. Review the threads on these drugs already posted in the forum - its good to know what people have said and experienced already.

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Canagliflozin or Empagliflozin which would you choose

As RapAdmin mentioned, Cana was used in the IPT. It also seems as if Cana has more (is the only one?) with SGLT1 inhibition and not just SGLT2 inhibition (see eg paper below). Not familiar enough with the pathways to comment on how much that may or may not matter re longevity pathways.

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“Canagliflozin remained distinct, likely because of its bioavailability,”

My decision to take Empagliflozin was influence by this article, as I have a mildly decreased GFR using Cystatin.

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