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:
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
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.
It could also be this
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.”
A new study on empagliflozin:
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.
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.
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.
“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.
Does anyone know when Empa will be available as a generic in the US? I think its still on-patent, so only Jardiance is sold in the US…
2027 according to this website:
Every time I take Canagliflozin, my urine turns very cloudy. It’s not painful but it’s scary looking. If I stop it goes away. Do you think it’s just causing a urinary tract infection?
Canagliflozin causes an increase of sugar/carbs being discharged via urine. My friend a pharmacist said this is why there is a slightly higher risk of urinary tract infections (its pretty small as a percent, and perhaps mostly in women). The higher sugar is something that bacteria like.
But - I just looked at this and it suggests you should talk to your doctor if you get cloudy urine: Canagliflozin (Oral Route) Side Effects - Mayo Clinic
Does anyone else here experience this?
Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control
“In this review we focus on the possible effects of SGLT2 inhibitors on different body systems. Beyond the diabetic state, SGLT2 inhibitors have revealed a demonstrable ability to ameliorate cardiac remodeling, enhance myocardial function, and lower heart failure mortality. Additionally, SGLT2 inhibitors can modify adipocytes and their production of cytokines, such as adipokines and adiponectin, which enhances insulin sensitivity and delays diabetes onset. On the other hand, SGLT2 inhibitors have been linked to decreased total hip bone mineral deposition and increased hip bone resorption in T2DM patients. More data are needed to evaluate the role of SGLT2 inhibitors on cancer. Finally, the effects of SGLT2 inhibitors on neuroprotection appear to be both direct and indirect, according to scientific investigations utilizing various experimental models. SGLT2 inhibitors improve vascular tone, elasticity, and contractility by reducing oxidative stress, inflammation, insulin signaling pathways, and endothelial cell proliferation. They also improve brain function, synaptic plasticity, acetylcholinesterase activity, and reduce amyloid plaque formation, as well as regulation of the mTOR pathway in the brain, which reduces brain damage and cognitive decline.“