#462

And just noticed that one of the other authors of that paper with SGLT as top gerotherapeutic is

Who now is the Chief Science Officer at Hevolution…

https://hevolution.com/en/web/guest/w/our-management-team

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#463

Yes, this paper was among the main ones that convinced me. I contacted Dr. Felipe Sierra about computational drug repurposing and whether we could use AI to screen medical records and analyze compounds at the molecular level to identify candidates for longevity. He never got back to me :sweat_smile:

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#464

I know people well who know him well. DM me if you want to discuss your proposal and we can see if it might fit the interest of those people and whether they perhaps can help you get in contact with him.

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#465

Unfortunately I think you are right. Too bad because I really would like to know more about the relative importance of SGLT1 vs SGLT2 inhibition.

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#466

There is a product called Calocurb that looks interesting https://www.calocurb.com/

#467

What is the active ingredient?

This is all they say…

The active ingredient in Calocurb is derived from a rare, New Zealand grown hops flower recognised for its high levels of Alpha acids. We have long known that bitter compounds with high levels of Alpha acids can support a feeling of fullness.

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#468

The active ingredient is called Amarasate.

This link has some info How Does it Work - Shop Calocurb Online | Calocurb US – Calocurb.com

Jay Campbell had a recent podcast on Calocurb and said as an appetite suppressant it’s as strong as Tirzepatide (Mounjaro). I haven’t tried it yet but will soon.

#469

I think thats just the registered trademark name of the product from the company, not the actual chemical or compound name (its like quoting the brand name “Rapamune” vs. the compound name (Sirolimus / rapamycin). If you know the actual compound, please let me know.

I searched on Pubmed on this, and there is only one study (which in itself is a little amazing…how many compounds only have a single study?)

Seems like pretty flimsy evidence - a single study with 30 people, (for comparison, there have been over 1400 research papers published on rapamycin / sirolimus).

It may be worth a try/risk if you are desperate and can’t afford/get more proven options. But this issue here is that there are probably thousands of compounds with a single study showing positive benefits, so if you only require a single study before you try something, you basically open yourself to thousands of compounds and you’ll quickly spend all your money…

On the positive side, the study is from “New Zealand Institute for Plant and Food Research Ltd. (PFR), a New Zealand government-owned Crown Research Institute” so I trust it more than some random company research study.

But here it is:

New Zealand Bitter Hops Extract Reduces Hunger During a 24 h Water Only Fast

Thirty adult men were recruited and required to fast for 24 h from 18:00 h to 18:00 h on the same day of the week for three subsequent weeks. Treatments of either a placebo or one of two doses (high dose; HD: 250 mg or low dose; LD: 100 mg) of a bitter hops-based appetite suppressant (Amarasate®) were given twice per day at 16 and 20 h into the fast.

These data suggest that appetite suppressant co-therapy may be useful in reducing hunger during intermittent fasting, and show that bitter compounds may regulate appetite independently of meal timing.

Conflicts of Interest

The authors themselves declare no competing financial interests. The New Zealand Institute for Plant and Food Research Ltd. (PFR), a New Zealand government-owned Crown Research Institute, has a licensing agreement with Calocurb Ltd. to commercialize a hops extract as a dietary supplement. A PFR internal funding source financially supported the project, but had no involvement in the collection, analyses, or interpretation of data; the drafting of the manuscript, or in the decision to publish the results.

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#470

Just found this article…

“The side effects that some customers might experience are generally associated with a laxative effect…”

Tell me about it, Calocurb! I had a similar experience after eating unpasteurized milk products in Calcutta. To be fair, while the diarrhoea lasted for a few days in India, it was only an issue for a couple of hours after my fourth dose of Calocurb. But in both cases I sat upon the porcelain throne wondering if the people in the stall beside me would think I was attempting to run a deep bath.

So in order for their calorie-restricting chemical to take effect, you need to first ingest calories, in order to avoid blowing your intestinal system into smithereens. OK. As an American colleague of mine commented, “cholera is also a superb weight loss intervention. What will they think of next?”

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#471

Ad discussed elsewhere GLP up => Insulin up.

If obese or diabetic it might be worth it for the weight loss and glucose control

For optimal longevity insulin up may not be good

So other options like SGLT inhibitors, acarbose and/or even metformin may be better alone or combined if longevity is the goal

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#472

  • is there thought to whether Cana + Acarbose will outperform either individually in males? It seems like a similar effect at a glance (lowers glucose spike, higher effect in male mice)

  • are any of the online rx sites (eg agelessrx, gethealthspan) supporting Cana yet?

#473

NMPA approves China’s second homegrown SGLT2 inhibitor janagliflozin

Jilin, China-based Huisheng Biopharmaceutical Co. Ltd. gained China NMPA approval for Huiyoujing (proline janagliflozin tablets), its independently developed sodium glucose transporter 2 (SGLT2) inhibitor for type 2 diabetes. The regulatory clearance, announced on Jan. 23, makes janagliflozin the second China-made SGLT2 inhibitor after Jiangsu Hengrui Medicine Co. Ltd.’s henagliflozin (SHR-3824), which was launched domestically in May 2022.

Papers:

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#474

Would you dare risk it?

#475

not me, just because there is many other SGLT2 inhibitors already out there. Had it been one of first I would have no problem trying.

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#476

These are the current prices from Jagdish. They all look about the same price. Which one is optimal for longevity? Thoughts?

@adssx What do you think?

1- Jardiance 10mg Tablet; Empagliflozin (10mg) = 8 USD for 10 tablets

2- Jardiance 25mg Tablet;Empagliflozin (25mg) = 9.6 USD for 10 tablets

3- Invokana 100mg Tablet , Canagliflozin (100mg) , Johnson & Johnson Ltd = 8 USD for 10 tablets.

4- Forxiga ,Dapagliflozin

5mg Tablet =11 USD for 14 tablets in 1 strip

5- Forxiga , Dapagliflozin

10mg Tablet =13 USD for 14 tablets in 1 strip

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#477

You can read a discussion between @adssx and me just a week or so ago above about reasons for why Cana vs Dapa/Empa might be better.

Starting here:

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#478

Yes, our previous discussions sum up the (lack of?) evidence for choosing the best option between cana, dapa, empa, and others.

Something else that might guide your decision (or not):

Canagliflozin was the first SGLT2 inhibitor approved in the US in 2013. Dapa and empa were approved in 2014. They have similar prices. So either AstraZeneca (dapa) and Boehringer/Lilly (empa) are way better at marketing their drugs than Janssen/Johnson & Johnson (cana). Or doctors are increasingly considering that empa and dapa are better alternatives for T2D, CKD, and HF.

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#479

If Cana was earlier its patents will be expiring earlier? The incentive to spend marketing dollars today depend on how many years a new patient the drug company requires will generate cash flow while they are under patent.

So if drug A has 3 years of patent left, but drug B has 7 years left of patent, the company that owns drug B be should be spending much more on marketing even if they are not better at marketing.

Might also be that the prescribing docs weigh the things that you are saying *but without taking into account

  • any longevity pathway aspects
  • the mendelian randomization data that suggests that SGLT1 (only in Cana of the ones listed above) decreases mortality
  • the repeat ITP results

(do most prescribing docs even know what ITP is or in many cases even know the the power of Mendelian randomization?)

Lastly, I think if we go by prescribing we should choose:

  • Metforming is better than SGLTi is better than Acarbose

While it seems that for a health optimizer with a meaningful exercise routine, the ranking for longevity is probably more

  • Acarbose > SGLTi > Metformin

(With Acarbose > SGLTi even more if one ways the side effect risks and/or for a person taking rapa)

So I don’t think looking at prescribing frequency from a sick care system for people who have T2D or other disease is all that informative for what we should do to optimize for longevity.

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#480

No, look at the dates of FDA approval below. We’re talking about less than 2y, not enough to create differences in marketing spending. In any case, generics are not yet available, so all big pharma companies continue spending like crazy on marketing before actual generic entry:

  • Canagliflozin: March 2012
  • Dapagliflozin: Jan 2014
  • Empagliflozin: August 2014

On top of that, canagliflozin arrived 2nd in Europe, and still, performs way worse there:

  • Dapagliflozin: Nov 2012
  • Canagliflozin: Nov 2013
  • Empagliflozin: May 2014

And here are the market shares in Australia. Yes cana is at 0 because they performed so badly that they left the market in 2015 (source):

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Here’s 2022 data about Central and Eastern Europe (CEE):

Empagliflozin (48.5%) was the most prescribed medication among SGLT2i, DPP4i, and GLP-1 RA; > 3 times more patients were prescribed empagliflozin than other SGLT2i (10 times more by cardiologists).

I’d love to see data in Japan, as canagliflozin was developed by Mitsubishi Tanabe Pharma. So maybe use is higher there.

No. Here we’re discussing drugs from the same drug class, approved more or less at the same time. Acarbose is not interchangeable with metformin. Whereas cana and empa are (long-term longevity benefits put aside ofc).

Anyway, again, I’m not trying to convince anyone. [Disclaimer: I’m taking dapa (because my doctor prescribed it), and I’m considering switching to empa (but I don’t think I could convince my doctor that there is any good reason to switch…).]

#481

Found it. Even in Japan, people are now (2021) using empagliflozin more: Jardiance remains in first place 2nd place is Farxiga, 3rd place is Suglat. Canagliflozin is not even 3rd, it’s ipragliflozin (trade name Suglat), another Japanese SGLT2i only approved in Japan and Russia. Ipragliflozin was actually the first SGLT2 inhibitor to be approved in Japan.

In 2016, canagliflozin’s inventor was proud to present it as the most used SGLT2 inhibitor in the world. Since then, all around the world, people have very quickly shifted from canagliflozin to dapagliflozin and empagliflozin. Why? My guess is that there is better data here and there for dapa and/or empa over cana. Not massive, but some small signals. For instance:

So these few data points/signals add up, and I guess gradually doctors come to believe (maybe incorrectly) that empa/dapa is superior to cana, at least for the indications they’re prescribed for, so T2D, HF, and CKD.

Are these doctors correct? Is empagliflozin really superior to other SGLT2 inhibitors for T2D, HF, and CKD? Does this extend to longevity properties? I don’t know :man_shrugging:

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