Recent Research on SGLT-2 Inhibitors, Canagliflozin, Empagliflozin, etc. - As cardio-renal protective agents

100% you will have gas, but I have lost several pounds

I spent a bit more for the brand name Jardiance (Empagliflozin) 25mg, 240.00 for 200 pills, including shipping through IndiaMART; I’m giving up on our US healthcare system!

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For me, too much gassiness and cramping. I just never adjusted to it.
Some people seem okay with it. Maybe a different gut biome?

Do you have much in the way of wheat-based products in your diet? I think this is the key problem associated with increase gas.

None so far. I am gluten free, no dairy, sugar etc perhaps my diet helps.

No, I tried avoiding wheat and it helped a little. Acarbose always gives me a bloated feeling.
Also, while it reduces blood sugar spikes, though because of my diet, I don’t usually have a large spike in blood sugar, it didn’t have any effect on my A1c level. So, I am going to see if canagliflozin lowers it. My doctor is not concerned about my blood sugar levels, but I am.

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Did the SGLT2 inhibitor help with your ankle swelling? I have it as well, have had 4 different doctors look at it (who did blood tests, MRIs, immune system tests, etc.) and tell me they had no idea what the problem is. I also have some swelling in my left hand, neither my ankle nor my hand were injured. I have been tested for CHF and heart issues and have been cleared of those as well. All my blood tests come back fine. I came across your post and am hoping for some good news.

Any thoughts on this research on Acarbose?

Association of Acarbose with Decreased Muscle Mass and Function in Patients with Type 2 Diabetes: A Retrospective, Cross-Sectional Study - PubMed.

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Yes, my ankle swelling went down. The reason for hand swelling may be a completely different problem from my bilateral ankle swelling after a day of sitting at work.

Yea, I have had them both looked at by many different docs and specialists and no one can tell me what the issue could be. It’s unilateral, but there is nothing with my heart, glucose and immune system that can explain it. I’ve learned to just cope with it, but I’d love a solution.

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Interesting, thanks for posting

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Dark teas include Qingzhuan brick tea, Kangzhuan brick tea, Liubao tea, and Ripen Pu-erh tea.

The authors agree that, as this is an observational study, their findings cannot prove that drinking tea improves blood sugar control. However, Dr. Wu did suggest why it might have this effect:

“These findings suggest that the actions of bioactive compounds in dark tea may directly or indirectly modulate glucose excretion in the kidneys, an effect, to some extent, mimicking that of sodium-glucose co-transporter-2 (SGLT2) inhibitorsTrusted Source, a new anti-diabetic drug class that is not only effective at preventing and treating type 2 diabetes but also has a substantial protective effects on the heart and kidneys.”

The research group is planning further investigations, as Dr. Wu told MNT:

“Our group is conducting a double-blind, randomized trial to further investigate the clinical effects of regular consumption of microbial fermented tea vs. black tea on glycemic control in people with type 2 diabetes, anticipating outcomes to be released in 2024.”

Puer tea is available in most Asian food stores.

Sample size is small. Effect is merely suggestive. But I like black tea. Puer tea has the same taste, despite the fermentation.

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@RapAdmin you stated that you may be on Canagliflozing (or other SGLT2 inhibitor) Acarbose. Could you give us an update what is your current mix of the said class drugs? I have access to all of them but am not sure what would be an ideal combination based on the most recent data. I have normal blood sugar. TIA.

Right now I’m out of empagliflozin but will be re-ordering (I transitioned from canagliflozin to empagliflozin due to side effect, details here: Canagliflozin for Anti-aging - One Month and 4 Month Updates

I also need to re-order acarbose. Generally I take acarbose when I’m going to eat a higher starch meal. I take empagliflozin on a low dose pulsed basis, one week on one week off (but no data really to support this, just trying it out and its been fine).

I don’t think we have any good data to suggest an evidence-based “ideal combination”. My general heuristic is to try to keep my fasting blood sugar low, and keep the post prandial BG spikes under 120. I also have normal blood sugar levels even without the medications.

Side effects are now minimal for these medications for me… little gas from acarbose (diet dependent) and nothing other than a little weight loss from empagliflozin (which is fine for me).

Related reading: Acarbose, An mTORC2 Promoter We Should All Take?

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Thanks always for all the fantastic information.

Here’s an interesting layman’s article on SGLT2 inhibitors

This article says interfering with sglt1 causes gastric upset so limiting the sglt1 impact of the major sglt2 inhibitors was by design.

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Yes, and according to the piece and one of its main refs, one of the main type of flozin that process led to was Cana. Ie the mix of SGLT2/1i that we know worked in the ITP longevity studies was from the type of SGLTi that was developed after the design principles in your quote above were applied.

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I have a hunch that SGLT2 inhibitors are the first rejuvenating drugs available. It’s just so impressive to just reduce deaths like that for heart failure, preventing kidney disease, etc. It’s also so random and no one knows how they work. Nobody is thinking rapamycin given to HF patients will reduce death rate. There is something magical about this.

Meanwhile, evidence grew that indirectly supported the safety of flozins for long-term use. In the 2000s, researchers discovered the cause of ​familial renal glycosuria, a condition that runs in families where patients have abnormally and persistently high levels of glucose in their urine, but have otherwise normal kidney function. They also have normal blood glucose levels and life expectancies, and report no complaints related to the condition.

It turned out that familial renal glycosuria was caused by genetic mutations ​in the SGLT2 gene that reduced the effectiveness of the SGLT2 pump, creating an effect similar to that of flozins. The fact that people could live completely normal lives with an impaired SGLT2 gene (and thus sweeter urine than everyone else) provided evidence that flozins, which artificially mimicked the condition, could be safely used in the long run.

This could be proven or disproven by looking at those affected by these genes.

I have a theory that it’s possible to alter your gut microbiome to suit acarbose better using acetic acid. (Apple cider vinegar).

Looking at gas reducing gut bacteria in the study below suggests acetates would be a byproduct of the gut bacteria you’d be after. And so using acv as a postbiotic to boost these before dosing with acarbose might solve the problem. You’d need to dose woth acv prior to initiating the acarbose though. And you’d probably want to titrate up the acarbose slowly.

See table 2 of https://www.sciencedirect.com/science/article/pii/S1756464622004376

This is just a pet theory, but very curious if someone wanted to try it.

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What difference would there be between 6.25mg and 12.5mg of empagliflozin in terms of HbA1c lowering and sugar excretion via urine? Would the beneficial renal and cardiovascular protection effects be seen with both doses?

Studies such as the following seem to suggest that the effect peaks around 10mg but the next lowest dose tested was 2.5mg…

Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple rising doses of empagliflozin in patients with type 2 diabetes mellitus - PubMed (nih.gov)