SGLT2 perspective a few years earlier -- interesting

I came across this 3y old thread and thought it was interesting and amusing given how we think about SGLT-2 now:

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It is interesting to hear that viewpoint.

I have, however, heard from other people that they think we should be thoughtful of the load on the kidneys though, as the person says “and the stress on the kidneys is higher”. One of the reasons I take a lower dose on the SGLT2 inhibitor vs. the higher dose. We do need to keep on top of the research as new studies are coming out all the time on SGLT2 inhibitors…

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Good point. I’d never considered kidneys as much as the higher risk for UTI with higher doses.

Do you know what the term for a “stressed kidney” is? Because, at least for diabetic kidneys SGLT-2 helps a lot. I’m not sure if there’s much work that’s looked at SGLT-2 effects of normally functioning kidneys

I’m just starting to research this also…

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are known to slow down progression of chronic kidney disease. However, theoretical concerns still exist that SGLT2 inhibitors could increase the risk of acute kidney injury.

Initiation of SGLT2 inhibitors sometimes induces a moderate transient decrease in estimated glomerular filtration rate (eGFR), probably due to amelioration of glomerular hyperfiltration via tubuloglomerular feedback.

This initial dip in eGFR is independent of the benefits from SGLT2 inhibition and is now considered reversible, but some clinicians are still concerned that patients taking SGLT2 inhibitors are susceptible to kidney damage induced by sepsis, hypovolemia, or nephrotoxic substances. This concern is mostly derived from the fact that a similar dip in eGFR is observed in patients at the initiation of renin–angiotensin system inhibitors, the use of which occasionally precipitates acute kidney injury (AKI)

and I guess generally we still have a lot to learn about SGLT2 inhibitors:

SGLT2 inhibitors reduce reabsorption of glucose and sodium in the proximal tubule, and, as yet, we know comparatively little about their mechanism of action for their potent clinical benefits. To what degree do the reduction of hyperglycemia, weight loss, and reduction of volume overload account for the clinical benefits (4)? Are the protective effects in the kidney responsible for the reduction in major adverse cardiovascular events? What is the contribution of the reduction in glomerular hyperfiltration via tubuloglomerular feedback, as elegantly shown by Vallon and Rieg (8) and Vallon and Thomson (9)? What are the potential contributions of redox biology, energy utilization, and immunosuppression? Are the benefits of this class of medications due primarily to inhibition of SGLT2 versus off-target effects? Answering these questions will not only inform our understanding of how best to treat patients but also our understanding of proximal tubular physiology and progressive CKD. It is likely that investigations into SGLT2 biology and these life-saving medicines will occupy the minds of basic scientists, clinical scientists, statisticians, and, importantly, trainees for years to come.

From Twitter today:

Sounds best to be a bit more conservative in its use.

It’d be nice if there were a way to regularly assess kidney functions that SGLT2 inhibitors might harm.

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The Fournier gangrene warning is in the package insert, but is extremely rare. Have to remember that the typical patient taking these meds is an obese diabetic with multiple comorbidities, so it seems reasonable to expect this phenomenon to be essentially non-existent in fairly healthy individuals taking it for life extension (knock on wood!).


Agreed - probably a very low risk issue for healthy people not suffering from diabetes, obesity, heart disease, etc.

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When would one want to consider taking SGLT-2 outside of prescription use, so for example would someone with a high fasting blood glucose but is not prediabetic benefit from taking them or is there an age to start(like rapamycin)?

There is no data that I’m aware of for SGLT2 inhibitor use in healthy populations (of humans). The key study we all refer to is the ITP canagliflozin study on mice that increased lifespan significantly - but we still lack human data… compared to rapamycin we have much less data on cangliflozin / SGLT2 inhibitors.

how has it been in your experience? I mean do you think it would be beneficial to take a young age or if you have higher fasting glucose levels?

From my experience, yes. They work extremely well at blood glucose control and I suspect its helpful for anyone, but I don’t have data to back it up. Low dose (e.g 100mg canagliflozin, or 10mg empagliflozin) will, I suspect, prove to be helpful to all adult males. Personal risk/reward tradeoffs may exist that we haven’t found though.

I will have to look into it more, but do people get their SGLT2 without a prescription same way as rapamycin (i.e. india)

Yes - the key benefit is that its much cheaper from India - $60/month vs. $600/month. Since we are healthy, we can’t get any insurance coverage of this medication.

Is this something that someone would take daily or weekly? I saw a post a couple months about someone saying that you do not need to take it daily.

You take it on the days you think you will be eating foods that will spike your blood glucose. On fasting or keto days you can skip it.

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Have you noticed any side effects or anything noticeable taking them? I just ordered 10mg empagliflozin tablets and was curious what I should look out for(if anything)

You will pee more… that is all.

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Have you tried taking it at night yet?
Also I got my empagliflozin from welcome healthcare and it came in today. It came about a week early.

What company from India?