Canagliflozin - Another Top Longevity Drug

[RapAdmin]

Canagliflozin: Significant Lifespan Extension Results in Male Mice

Results of the National Institutes on Aging, ITP study

Canagliflozin extends life span in genetically heterogeneous male but not female mice

• Increased median lifespan in the male mice by 14%, maximum extension of 9%
• But had no effect on the females

Canagliflozin is in the class of drugs known as SGLT2 inhibitors. SGLT2 inhibitors have been commercially available for over 10 years and they are used commonly in patients with type 2 diabetes as it blocks the re-uptake of glucose so that more glucose is excreted in the urine. They affect the process in the kidney that deals with very high glucose levels without having much scope for causing toxicity, so are safe from causing hypoglycemia.

While canagliflozin was the drug tested in these ITP studies, it is likely (but not yet proven) that all the drugs in the SGLT2 class of drugs provide the similar benefit of life-extension. The other SGLT2 inhibitor drugs (generic / brand names, and combinations with other drugs) are as follows:

• canagliflozinInvokana
• canagliflozin/metformin (Invokamet)
• canagliflozin/metformin extended release (Invokamet XR)
• dapagliflozin Farxiga
• dapagliflozin/metformin extended release (Xigduo XR)
• dapagliflozin/saxagliptin (Qtern)
• empagliflozin (Jardiance)
• empagliflozin/linagliptin (Glyxambi)
• empagliflozin/metformin (Synjardy)
• empagliflozin/metformin extended release (Synjardy XR)
• ertugliflozin (Steglatro)
• ertugliflozin/metformin (Segluromet)
• ertugliflozin/sitagliptin (Steglujan)

What could explain the sex-specific difference in the effect on lifespan?

The following information is sourced from the Peter Attia / Richard Miller podcast. Richard Miller suggested that when you take these canagliflozin results together with the acarbose results, you’re led to the inference that something about aging in the male mice depends a lot on staying away from really high glucose levels. However, whether that means that high glucose in the males triggers a circuit in the hypothalamus, which is bad for you or something, is just a hypothesis. It may be that it has to do with the susceptibility of the hypothalamus to inflammatory change differentially in males than in females. And this nebulous change has an impact on the cancer, or an impact on anti-cancer defenses or something. Rich Miller believes that these hypotheses are equally likely to be true, but at present, none of it gives us much of a hint as to why these drugs have a much more striking effect in the male mice

Graphical abstract of blood glucose response. [source]

Did Rich Miller see the same effect in Canagliflozin that they saw with acarbose in that the hemoglobin A1C was unaffected?

Rich’s recollection is that there was no difference in the effect on hemoglobin A1C in mice. This is surprising because it is affected in human diabetics.

Summarizing what we know about canagliflozin :

• We don’t know whether the positive effect of canagliflozin is due to its impact on glucose, SGLT2, or SGLT1
• The literature is showing, for example, that SLGT-2 inhibitors have an effect on tumors specifically, and other things like heart attacks, independent of whatever’s happening in terms of glycemic control
• The shortest, simplest explanation—that the benefits are due to canagliflozin’s effect on glucose—may not be right. — “There are other ideas that deserve a lot of exploration .”
• Peter Attia has said he is excited about the data coming out around canagliflozin : “We are very excited about this class of drugs clinically in our practice; the cardioprotection, renal protection, obviously the glycaemic benefits are all pretty exciting.”

Personal Experience and Observation with Using Canagliflozin for Anti-aging:
I have found that using canagliflozin (while taking rapamycin) for anti-aging is very effective in moderating glucose spikes. I use a continuous glucose monitor and while I was using canagliflozin my blood sugar levels seem to be well-moderated and mostly kept within the range of 80 to 110 mg/dL (approx. 3.9 and 6.0 mmol/L). I successfully tried canagliflozin for approximately 3 months and thought it was working well. However, at some point it became obvious I was suffering from an abnormal level of exhaustion and I stopped taking it - which I’ve reported on here:
Canagliflozin for Anti-aging - One Month and 4 Month Updates

Pricing and Availability

USA Prices:
Brand Name Product:
Canagliflozin (Invokana) Average Street Price: $650 for 30 x 300 mg tablets ($21 per 300 mg tablet)
GoodRx Discounted Canagliflozin (Invokana) Price: $550 for 30 x 1 mg tablets ($18 per 1 mg tablet)

Generic: Generic version of Canagliflozin Not Available Yet

India Prices:
(you can check current prices yourself via Indiamart.com - search on “Canagliflozin” for example.

Current exchange rate India Rupees to US $ is around 75:1 based on this currency exchange calculator

Approximate India Pricing:
Canagliflozin (Invokana) Price High: 1500 rupees for 10 tablets of 300 mg (approx. $2.00 per tablet
Canagliflozin (Invokana) Price Low: 1200 rupees for 10 tablets of 300 mg (approx. $1.60 per tablet)

Canagliflozin (Invokana) Price High: 700 rupees for 10 tablets of 100 mg (approx. $0.93 per tablet
Canagliflozin (Invokana) Price Low: 500 rupees for 10 tablets of 100 mg (approx. $0.66 per tablet)

Note: The India pharmacies have been amazingly good as far as delivering the medicines they promise. We’ve spoken to a many people who have ordered their medicines from India Pharmacies and everyone have had good experiences and always have received the medicine that they ordered. The only exceptions being that a couple of times people’s orders have been held up or blocked at US customs.

Most people taking Canagliflozin for anti-aging purposes report taking somewhere between 100mg per day (one dose per day) and 300mg per day (one dose per day) - taken once in the morning.

Cost of One Year of Canagliflozin:
The cost at the USA high end for 360 tablets, Canaglifliozin (Invokana) 300mg, is $7,800+
The cost at the USA mid-range for 360 tablets, Canaglifliozin (Invokana) 300mg, is $6,600+

The cost at the India mid-range for 360 tablets, Canaglifliozin (Invokana) 300mg , is $720
The cost at the India Low end for 360 tablets, Canaglifliozin (Invokana) 300mg, is around $576

The cost at the India mid-range for 360 tablets, Canaglifliozin (Invokana) 100mg , is $334
The cost at the India Low end for 360 tablets, Canaglifliozin (Invokana) 100mg, is around $237

Read the Research Paper on the Canagliflozin Longevity Study done by the ITP:

jciinsight-5-140019.pdf (1.5 MB)

Canagliflozin extends life span in genetically heterogeneous male but not...

Long-term efficacy and safety of canagliflozin over 104 weeks in patients...

Canagliflozin Indications and Dosing

[LeeJohn]

Thanks for your information

I eat Metformin 500mg/day, I tried to increase dose to 1500mg/day
But everytime I tried then failed, I can’t tolerate Metformin more than 500mg, it made me very nausea

After seeing your introduction of Canagliflozin, and some light research, I am excited to try Metformin + Canagliflozin combination

The plan is to get Canagliflozin from Indiamart, but I am not very familiar with it
You said that current Canagliflozin 300mg price is between: $1.60 per tablet ~ $2.00 per tablet

@RapAdmin

Approximate India Pricing:
Canagliflozin (Invokana) Price High: 1500 rupees for 10 tablets of 300 mg (approx. $2.00 per tablet
Canagliflozin (Invokana) Price Low: 1200 rupees for 10 tablets of 300 mg (approx. $1.60 per tablet)

[RapAdmin]

Welcome to the site - thanks for posting a question.

First of all - have you tried the extended release version of metformin? I’ve heard it seems to help with the issues you mentioned. When I was taking metformin, that is what I took and never had any issues.
https://www.mayoclinic.org/drugs-supplements/metformin-oral-route/side-effects/drg-20067074?p=1

Ultimately - I decided to stop taking metformin because it didn’t have much in the way of lifespan improvement in the National Institute on Aging ITP program clinical trial: See this podcast and notes:
https://www.listennotes.com/podcasts/the-peter-attia/148-richard-miller-md-phd-He5Bsxw_XyN/

• The failure of metformin: reconciling negative results of the ITP with data in human studies (1:42:30);

Also - Metformin seems to have some issues related to decreasing / blocking muscle growth when you exercise:

Metformin offers no strength training benefits for seniors, study shows

Metformin blunts muscle hypertrophy in response to progressive resistance...

With regard to canagliflozin and indiamart vendors… Indiamart is just an online “mall” of different retailers and vendors - you don’t actually buy anything from Indiamart - you just use the platform to find different companies selling things in India.

My approach a few years ago was to try different vendors with smaller orders to see what happened. Every single vendor I’ve tried - somewhere between 8 and 10 vendors total - delivered exactly what they said they would deliver. No issues. And, many other people seem to have the same experience generally, who have shared their experiences with me. I’ve seen one person who said they did not get their order - so like all resellers online - some are flakey, but it seems rare.

You can do some due diligence on the vendor’s website by checking using this website:
https://www.scamadviser.com

I’m not sure how good scamadvisor is, but its a start.

Also - see the posting on our site that covers medicine importing here:

Importing Rapamycin to Save Money (pt 2)

[ImportedWide5] As we’ve mentioned elsewhere on this site, because drugs like rapamycin for anti-aging are not covered by insurance, people are increasingly looking outside their home countries to purchase them. Specifically, people are looking for the best value (i.e. lowest prices) for their prescription medications due to the high cost, especially in the USA. The US has the highest drug prices in the world due to the combined effects of lack of competition and limited regulation (due to lobbyists). Below is the process that people are communicating to us has worked well for them to obtain the lower cost medications, specifically rapamycin (sirolimus). Please also see the 4-page Valisure Lab analysis performed on the rapamycin (Biocon Rapacan and Zydus Siromus) from India that one user…

As far as the specific Canagliflozin and pricing - that sounds like a good price. Generally people look at 2 or 3 vendors who seem to have good prices and compare them based on the questions outlined in the “How People Import Rapamycin” page overview.

I generally focus much more on the brand/manufacturer of the actual medicine, and care too much about the specifics of the pharmacy/reseller. People talk / email with the reseller and get information on the company and product but I change resellers frequently and focus on price, availability and have not had any problems.

Oh - one other thing, you should be aware of the key side effect risks of canagliflozin. There is a slightly higher risk than placebo of urinary tract infections due to the higher sugar content of the urine when taking this medication.

Side Effects of Invokana (Canagliflozin Tablets), Warnings, Uses

I hope this helps answer your question. As always, work with your doctors to make sure this is a good medication for you.

[LeeJohn]

That’s really thorough guide, very appreciate your work

Yes I’ve tried extended metformin, and it has less side effect.
But I exercise everyday, I don’t want to inhibit mTor all the day. Extended form may limit exercise benefit
So I use immediate-release form before bed, then exercise in the afternoon, hoping metformin not interfering exercise too much

ITP result of Metformin is a bit disappointing. I am waiting for TAME trial
Before a more conclusive result of whether Metformin can extend lifespan of human, I may still use Met, but in low dose

Hence the ITP result of Canagliflozin is exciting
This article suggests Metformin + Canagliflozin may be an option to try

Fixed-Dose Combination of Canagliflozin and Metformin for the Treatment of...

Thanks for sharing your experience in IndiaMart, that’s really help
Following your guide, I will buy 240 tablets from this reseller ( Invokana Canagliflozin 300mg $0.63 per tablet), and to see if the drug is true. Then alternate other reseller next time

For the urinary tract infections risk of Cana, I will take probiotic and D-mannose to reduce infection likelihood
I choose these two probiotic brands (Based on the Labdoor ranking Labdoor - Best Probiotics Supplements, and price consideration)
Schiff Digestive Advantage Daily Probiotic
Garden of Life Primal Defense Ultra Probiotic Formula
(If you have other good probiotic to recommend, please let us know)

This Forum is a gem!
Really appreciate your work again

[LeeJohn]

Update:

I’ve ordered 240 Canagliflozin tablets from “Marksans Pharma Limited” in “IndiaMart” weeks ago
( Invokana Canagliflozin 300mg, $0.63 per tablet)

Today I received a email from Sureroute Courier Services (shipping company)
He said my good had been intercepted in airport
I need to give him NOC/INSURANCE CERTIFICATE or pay fine of US$148.00

Here is the email:

=========================

Dear Customer,

We wish to bring to your notice, that your parcel with reference number
XXXXXXXXXX(I hide it for private information) from Marksans Pharma Limited India, is on hold at Beijing
Capital International Airport, China, where security operatives had
intercepted it demanding for NOC/INSURANCE CERTIFICATE or fine of
US$148.00 before they can allow it for further shipment.

You are requested to transfer the above amount to our branch office in
India where your parcel was dispatched from to enable us use the company
payment gateway to reconcile with the airport authority and recommend
for the immediate release of your parcel.

Use the below payment details to send payment to our branch
office India where your parcel was dispatched from:

PAYMENT DIRECTION:
Receivers first name: Nirmala
Receivers last name: Saud
Receivers amount: US$148.00
Receivers country: India
Receivers address: Andheri (West), Mumbai, Maharashtra 400053
Via: Western Union, MoneyGram or RIA Money

Regards
Sureroute Courier Services.

=========================

I suspect it’s a fraud
I also suspect this IndiaMart reseller is an accomplice

I already wrote an email to this IndiaMart reseller, ask him what happened to the shipping
But no response yet, still waiting…

I wonder anyone have met this situation?
What Should I do? any suggestion?

[RapAdmin]

This is really bizarre at many levels. To what country are you trying to ship it to?
When shipping to the USA I’ve only ever heard of people using IndiaMail SpeedPost EMS, or DHL or Fedex - for shipping. So I find it very strange that a courier company is being used. did you agree to that before hand? Usually people ask the shipping price options from the pharmacy - and specify the one that works best for them as outlined in the “Importing Rapamycin” post.

Usually its about $15 or $20 for the package being shipped by SpeedPost/EMS, and more expensive via DHL and Fedex.

Did you agree to that courier service before hand? Why did you choose that courier service?

If you are importing to another country - then it could be different.

[LeeJohn]

Yes I agree that’s really bizarre

I live in Taiwan
This IndiaMart reseller did ask me the country, then told me the shipping cost to my country is $43
He didn’t mention the shipping company, so I didn’t know he uses Courier Service as shipping company

Last time I bought rapamycin from another IndiaMart reseller(Varun Medicals, if anyone wants to know), the shipping cost is $40 via EMS by the way.

And I successfully got the rapamycin within 3 weeks from Varun Medicals.

But this time I forgot to ask him(Marksans Pharma Limited) the shipping company
I should read your “Importing Rapamycin” more carefully!

I will update the progress
And share the experience to people who want to buy medicine on IndiaMart too

[AlexKChen]

So which India pharmacies work, and which ones work through methods other than wire/bank transfer? (all of those impose extra fees if you come from the US).

[RapAdmin]

All in the list seem to be good (have been used by 1 or more people with successful results) - but I think pretty much all of them require a bank wire transfer or money transfer using something like wise.com or tazapay.com, etc.

List of Reliable Online Pharmacies for Buying Rapamycin, etc

Below are some vendors that users here say they have received shipments from without problems and without need for a prescription. Results may vary by country being shipped to due to different importation rules and regulations. Before you order, review the import process that people have used: Importing rapamycin details. Also, we recommend you work with your doctor for any medications you are taking: Rapamycin Prescribing Doctor List Pricing: For comparison’s sake, the lowest prices in the USA for generic sirolimus seem to be coming out of the Amazon (prime) pharmacy. As of Dec/2021 the price is $742 for 90 tablets of 2mg, for a total of 180mg. So, a price of $4.12 per mg. (Obviously, with Amazon pharmacy you need a prescription). Sometimes I’ve seen the amazon 90 tablet / 2mg price…

[RapAdmin]

Perhaps of interest to people:

Lower Blood Sugar Levels Extends Lifespan - SGLT2

[CTStan]

How do you minimize risk, which although is low can be serious? Is there a change in the urinary environment which increases the possibility of UTI or genital infection? If so, is that related to the amount of sugar excreted and therefore the importance of diet in avoiding such risk? If not, what is the mechanism and what, if anything can be done to minimize the risk associated with canagliflozin? And since a known rapamycin risk is the possibility of bacterial infection, are we setting up a higher risk situation by taking rapa and canagliflozin together?

[RapAdmin]

These are all really good questions, and I think we do need to try to get answers to them.

I may be wrong, but my thinking is that the UTI risk is higher for females, so I’ve been less concerned about that (as a male).
I also take a lower dose (10mg of empagliflozin) - and do it in a pulsed dosing - approx. 3 weeks on, 1 week off. Not that there is any research to support this approach.
I also have Azithromycin on hand if I get any bacterial infections - so can immediately start taking it if I do have any problems.

[CTStan]

I just priced Canagliflozin at Alldaychemist. $2.20 per 100 mg tablet. They are reliable, but that is quite a bit higher than what I was expecting. Are there any other proven reliable India pharmacies?

[RapAdmin]

See our list of reliable online pharmacies

Check out canagliflozin and empagliflozin

[Rapasailor]

@RapAdmin What do you think about taking Canagliflozin PRN, on days when the diet is planned to be less than optimal? Do you see it working quickly enough to matter on your CGM? I use enough carb restriction to not need it on most days, but then there are days when I know I’m not going to be good. Acarbose PRN has led to some awful gastric upset, so I’m not using it any longer.

[RapAdmin]

Here is my experience with canagliflozin:

Canagliflozin for Anti-aging - One Month and 4 Month Updates

I’ve been taking 10mg empagliflozin for the past two months and its been going well. It has a big impact on flattening gluocose spikes, which seems to be a good thing for anti-aging (in males). I generally try to avoid processed foods and simple carbs - but do eat a lot of salads which can sometimes have a higher carb load, or some fruit like apples, which I like.

I also dose acarbose occasionally with meals when I haven’t taken empagliflozin or later in the day if I’ve taken empagliflozin earlier in the morning - but have the same issue as you with acarbose - a lot of gas most of the time, so its far from optimal.

[AlexKChen]

https://www.goodrx.com/sglt2-inhibitors

Wow these are super-expensive outside of India

[RapAdmin]

Yes… $600 per month vs $60 a month from India.

[shc]

I’ve been taking it on an as needed basis too. This is because I’ve read reports of fatigue and because SGLT2i selectively reduce levels of blood glucose only when it is high.

So at least as far as the CGM related benefits go, I don’t see a need unless there’s a high carb meal.

I however don’t know about other benefits or disadvantages. I’ve imagined that the cardioprotective and renal-protective properties of SGLT2i are downstream from lowering the blood glucose. But I might be wrong.

[RapAdmin]

Dr Brad Stanfield believes SGLT2 inhibitors will be first longevity drugs prescribed by clinicians.

Despite his views on supplements, Stanfield believes that there are systems in place to allow longevity interventions to end up in clinical use, especially the Interventions Testing Program run by the US National Institute on Aging. He cites results seen in SGLT2 inhibitor Canagliflozin as an example.

“The Interventions Testing Program reported a median 14% lifespan extension in male mice with this medication,” says Stanfield. “That’s very interesting, but needs more work, and that work is being done in the clinical field.”

SGLT2 inhibitors are already being used to treat Type 2 diabetes, but Stanfield says clinical work is now indicating that these medications could also have an impact in heart failure, chronic kidney disease and weight loss.

“In terms of a so-called longevity medication, I think that SGLT2 inhibitors will be the first ones that will be prescribed and made widely available. That’s because they appear to provide significant protective effects for the kidneys. Our kidney function starts to decline from around the age of 30, so if we can use SGLT2 inhibitors to slow down or prevent that decline, that would be a powerful intervention. Of course, we’re waiting on the human data to come through, but there is a robust way of these things getting through to people.”

Read the full story:

We need an evidence-based approach to longevity and healthspan