Canagliflozin - Another Top Anti-aging Drug

#382

Oh, no question, ordering off-patent medications rom Europe would be much safer and better… if it could be accomplished. The issue is that (unlike India) these countries have well-functioning healthcare and legal systems that are optimized to serve their populations - and selling drugs to people outside of the EU is likely not legal or certainly not as easy as ordering from India.

But perhaps if you have a prescription it might be possible in some areas… for example perhaps you could get a prescription from EuDoc using a friend’s address in Europe, then with that prescription buy medication from an online European pharmacy, have it shipped to a friend in Europe, and then have it shipped to you in the US by your friend. Just brainstorming here…

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#383

Germany is the only country in EU that allows sending prescription medicines.
The only other possibility is that ypu get a prescription and a friend who fills it in pharmacy and sends it to you, but medicines shouldn’t be declared as they are forbidden to send in and out of EU.

PS I should add that Germany has highest medicine prices in EU, e.g. rapamycin is usually around 120-140 EUR for 30x1mg in most EU countries, in Germany it is almost 500 EUR…

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#384

I believe only dapaglifozin is generic.

#385

You’re right. Even that may be hard. European doctors rarely prescribe off-label: they mostly follow national guidelines. So you’d struggle to get a prescription for anything “exotic” first (I include SGLT2 inhibitors in “exotic” drugs, for someone without T2D/CKD/HF).

You could try to buy from non-EU European countries like Serbia, Kosovo, Montenegro, Ukraine, and Turkey. But I am not sure it would be much safer than India (I would trust Turkey though). And these products may not even be approved and available there.

Yes, dapagliflozin is generic in Canada, the US and the EU but in the US the generic cannot be sold until October 2025.

In November 2023: Lupin Receives Tentative Approval from U.S. FDA for Canagliflozin Tablets

Same for empagliflozin in the US: US generics launch and approval for Dr Reddy’s and Lupin

Ertugliflozin is also approved as generic in the US: First Generic Drug Approvals | FDA

It looks like empa and cana are not generic in the EU though.

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#386

I think I’d read somewhere that Indian meds are good quality, plus I was surprised to read that a few of big pharma actually make their medicines in India. So far everything I’ve bought from India has been good (meaning it has had the desired/supposed effect)

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#387

Empagliflozin improves mitochondrial dysfunction in diabetic cardiomyopathy by modulating ketone body metabolism and oxidative stress

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Open access article:

https://www.sciencedirect.com/science/article/pii/S2213231723004111

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#388

Any sense on when and from where (normal pharmacy’s?) they will actually be available in the US?

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#389

No idea on the Lupin product launch. I’m sure we’ll hear about it when it becomes available (and it will show up at places like CostPlusDrugs.

Some other related news:

SGLT2 Inhibitors Appear Protective Against GI Cancers

Results of a global network database of patients with type 2 diabetes suggest that sodium-glucose cotransporter-2 inhibitors could reduce the incident risk for gastrointestinal cancers except pancreatic cancer. In a comparison of SGLT2 and dipeptidyl peptidase-4 inhibitors, patients started on SGLT2 inhibitors had almost a 15% lower risk for these malignancies.

The study showed protection against cancers of the colon, esophagus, stomach, small intestine, rectosigmoid junction, rectum, anus, liver, bile duct and gallbladder among the 1,412,780 individuals drawn from 92 U.S. medical centers in the TriNetX database of more than 200 million patients.

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Full Story:

https://www.gastroendonews.com/PRN/Article/12-23/sodium-glucose-cotransporter-2-inhibitors-gastrointestinal-cancers/72224

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#390

Here’s the paper: S321 Lower Incidence of Gastrointestinal Cancers in Sodium Glucose Co-Transporter-2 Inhibitor-Treated Patients With Type 2 Diabetes Mellitus: A Population-Based Cohort Study in the United States

Too bad the authors did not look at the dose relationship and at each SGLT2. Does more/longer SGTLi use prevent cancer more? Which SGLT2 is best?

This paper is also good: Sodium‐glucose cotransporter 2 inhibitors versus dipeptidyl peptidase 4 inhibitors on new‐onset overall cancer in Type 2 diabetes mellitus: A population‐based study

To the best of our knowledge, this is the first territory‐wide study that does a direct comparison of the effect of SGLT2I and DPP4I on overall and pre‐specified cancer risk in a cohort of Asian patients. The main findings of this study are as follows: In comparison with DPP4I,
(i) SGLT2I were associated with a lower risk of all‐cause mortality, cancer‐related mortality and new‐onset overall cancer;
(ii) SGLT2I were related to a lower risk of new‐onset breast cancer;
(iii) when stratified according to the medication subtype, dapagliflozin and ertugliflozin both demonstrated a reduced risk of new‐onset malignancy, with the former also presenting with a lower risk of breast cancer.

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#391

Potentially another SGLTi super power (weak data/signal for now, more research needed…):

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#392

Is this a good price, have never bought before. Seems a bit high, NO?

200 tablets Empagliflozin 25 mg - $ 160

Thanks,

#393

I wish that was true.

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#394

Invokana 100mg Tablet , Canagliflozin (100mg) , Johnson & Johnson Ltd = 7.5 USD for 10 tablets.

My last quote from Jagdish

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#395

As fas as I am concerned i only care if it is generic in India. Very good chunk of people on these boards order from India. I have to assume though that if it is not generic yet in USA it can’t be produced/generic in India either?

#396

that’s pretty cheap, plus the real deal from J&J. I was more interested in Indian prices, since I don’t want to bother to go through a doc at home.

#397

Are you sure that is not some for of copay, this is what shows in search results: more like $20 per pill here in USA lol

CVS Pharmacy

Invokana

30 tablets 100mg

Logo of CVS Pharmacy

$619.93

BINPCNGroupMember ID

009893DCAE1RXGD6KU609576

#398

I updated my post to indicate that was the quote from Jagdish (India).

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#399

Same. I order from there a lot and never once was disappointed

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#400

Your daily dose of recent SGLT2 papers:

Study funded by the UK Medical Research Council (government body): Safety and effectiveness of SGLT2-inhibitors in people with type 2 diabetes over 70: UK population-based study using an Instrumental Variable approach. Not yet peer-reviewed, but it confirms the “very low” DKA risk, even among T2D (and especially among people less than 70yo). Unfortunately, no side-by-side SGLTi comparison in the paper:

Risk of DKA was increased with SGLT2-inhibitors in those aged ≥70 (Incidence risk ratio compared to DPP4i: 3.82 [95%CI 1.12,13.03]), but not in those <70 (1.12 [95%CI 0.41,3.04]). However incidence rates with SGLT2-inhibitors in those ≥70 was low (29.6 [95%CI 29.5,29.7]) per 10000 person-years. […] DKA is a rare AE and the risk increase with SGLT2-inhibitors may be restricted to adults over 70 […] Although we found DKA risk with SGLT2-inhibitors was elevated in those over 70, incidence was very low. […] SGLT2-inhibitors in older adults are effective and do not increase risk of dehydration, falls or urinary problems in older adults with T2D. However, risk of genital infections is increased, and DKA is a rare but severe adverse event of concern, meaning baseline DKA risk should be carefully assessed before initiation of SGLT2-inhibitors."

Meta-analysis of 17 RCTs (100k+ patients): GLP-1 receptor agonists, SGLT2 inhibitors and noncardiovascular mortality in type 2 diabetes: Insights from a meta-analysis 2024. (No side-by-side SGLTi comparison either. Similar results for GLP1RA btw, so they’re also quite good.)

Compared to placebo, SGLT2i significantly reduced noncardiovascular mortality (RR = 0.90; 95%CI: 0.82–0.99; I2 = 0 %; p < 0.05) along with cardiovascular mortality (RR = 0.84; 95%CI: 0.77–0.92; I2 = 28 %; p < 0.001).

Good review in the Journal of the American College of Cardiology: Hyperuricemia and Gout Reduction by SGLT2 Inhibitors in Diabetes and Heart Failure: JACC Review Topic of the Week 2024

SGLT2 inhibitors induce a state of starvation mimicry at a molecular, cellular, and physiological level, which is characterized by glycosuria and ketogenesis and by upregulation of nutrient deprivation signaling (ie, SIRT1) and downregulation of nutrient surplus signaling (ie, mTOR and HIF-1α). […] The actions of SGLT2 inhibitors to upregulate both SIRT1 and AMPK and downregulate both mTOR and HIF-1α are seminal to their cardioprotective and nephroprotective effects.

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Small study trying to understand why and how SGLT2i improve outcomes: Empagliflozin Improves Vascular Insulin Sensitivity and Muscle Perfusion in Persons with Type 2 Diabetes 2024

Following empagliflozin, insulin infusion improved endothelial function (p=0.02), lowered peripheral and aortic systolic (each p<0.01), diastolic (each p<0.05), mean arterial (each p<0.01), and pulse pressures (each p<0.02), altered endothelial biomarker expression, and decreased radial artery forward and backward pressure amplitude (each p=0.02). Empagliflozin also improved insulin-mediated skeletal and cardiac muscle microvascular perfusion (each p<0.05). We conclude that empagliflozin enhances insulin’s vascular actions which could contribute to the improved cardio-renal outcomes seen with SGLT2i therapy.

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#401

Can you comment on this - ages, genders, overall risk levels?