How can Empagliflozin remove 90g of glucose per day?

[Rabdos]

Hello!

I read Empagliflozin removes 90g of glucose per day.
How it can do that? I mean after a meal the blood glucose can be 250mg/dL. That is 12.5g in the whole blood and you cannot go lower than 100mg/dL which is 5g in the whole blood. So Empagliflozin could only remove 7.5g of glucose after a meal.
If you eat 3 times per day, that is 22.5g of glucose per day.

How does it supposedly remove a huge 90g of glucose without dropping you into hypoglycemia?

Are my calculations wrong?

Thanks!

 

[ickihun]

I'm no expert but those meds filter using the kidneys and are prone to acidketosis. My belief is it reduces circulatory blood hence meter tester shows one reading but new glucose is not reduced resulting in very high glucose about to affect the system. A few people hv suffered a severe hyperglucemic event. Warnings are now on meds and GPS hv sent letters to any patient using similiar meds.

 

[bulkbiker]

Are you sure its not 90% rather than 90g

from the wiki page on it

Has a nasty list of possible side effects..

https://en.wikipedia.org/wiki/Empagliflozin

 

[Brunneria]

Hello!

I read Empagliflozin removes 90g of glucose per day.
How it can do that? I mean after a meal the blood glucose can be 250mg/dL. That is 12.5g in the whole blood and you cannot go lower than 100mg/dL which is 5g in the whole blood. So Empagliflozin could only remove 7.5g of glucose after a meal.
If you eat 3 times per day, that is 22.5g of glucose per day.

How does it supposedly remove a huge 90g of glucose without dropping you into hypoglycemia?

Are my calculations wrong?

Thanks!

Hi Rabdos.

Just because someone has a certain amount of glucose in the blood at any one time, doesn’t mean that they only have that amount of glucose throughout the whole day.

I think you would be better thinking of it as glucose passing through the bloodstream. Like cars on the road. There may only be 200 cars on a stretch of road. But those cars join and leave the road all the time as they travel to where they are going.

So over a couple of hours there may be 1000s of cars that pass along the road.

 

[ringi]

Think of how much glocose the liver releases into the blood everyday, then think of how much comes from eating carbs that all get digested into glocose and transported by the blood.

 

[LittleGreyCat]

Hello!

I read Empagliflozin removes 90g of glucose per day.
How it can do that? I mean after a meal the blood glucose can be 250mg/dL. That is 12.5g in the whole blood and you cannot go lower than 100mg/dL which is 5g in the whole blood. So Empagliflozin could only remove 7.5g of glucose after a meal.
If you eat 3 times per day, that is 22.5g of glucose per day.

How does it supposedly remove a huge 90g of glucose without dropping you into hypoglycemia?

Are my calculations wrong?

Thanks!

90 grams per day is less than 4 grams per hour or 0.07 grams per minute.
So that would be the rate that sugar was extracted from the blood and passed into the bladder in the urine.

Remember that glucose is always coming into the blood stream and leaving it by going, for example, into the muscles and into fat.
Insulin is taking it out all the time.

This is just a small extra trickle of sugar leaving the blood stream by another route.

 

[Rabdos]

I still believe my question is valid. 70mg of glucose per minute is huge given that the whole blood has 5g of glucose! This means that every 1 hour, empagliflozin removes from the circulation the total amount of glucose in blood! This is in addition to the glucose consumed by the tissues! This means that this glucose must be replenished internally (excluding food ingestion empagliflosin would still need to remove 60g of glucose as I explain below). This is very aggressive glucose removal and maybe that's the reason behind empagliflosin's unique ability to decrease morbidity and mortality.

We normally eat 3x100g of sugar per day in three meals. After 90min from ingestion, the blood glucose tops at around 250mg/dL. This means that from the 100g of sugar ingested, only the 12.5g ended up in blood as excess. The rest have been absorbed.

During these 90min, empagliflozin would have removed 6.3g of sugar. In every meal, empagliflosin would remove 6.3x3= 19g of sugar.

Unless it removes more during high blood glucose period which is understandable if its removal is related to the blood glucose levels. Let's say it is proportional. So if at 100mg/dL, empaglifrozin removes 19g of sugar per 4.5h, then for 175mg/dL it would remove 19x1.75 = 33g of glucose per 4.5h. I take 175mg/dL and not 250mg/dL because I take the average as the postprandial glucose rises gradually.

This means that Empagliflozin will need to remove a whopping 60g of sugar in the rest day that there is supposedly normoglycemia!

I suspect that this may be the reason for empagliflosin's success in decreasing mortality and morbidity. It must remove significant glucose from the blood during the whole day. This would mean that the therapeutic target for diabetes should not be normoglycemia but severe and constant glucose restriction!

What do you think?

EDIT: Actually, I think to be more accurate, this would be the equation of empagliflosin glucose removal with R=glucose removal rate per hour:

15xR +9xRx1.75 = 90

15h times the R during normoglycemia
plus
9h times R during feeding period times 1.75 as the average factor of blood glucose increase (I took 3h per meal to double the 90min as I assume normoglycemia to return after 3h)

the above sum equals the 90g of glucose removed per 24h

This means x = 2.92g of glucose per hour which means that every two hours of normoglycemia, empagliflosin removes the whole glucose in the blood!

 

[Rokaab]

I read Empagliflozin removes 90g of glucose per day.

Where?
I'm asking because you may be looking at it in the wrong context especially because as diabetics we don't normally measure in actual grams of glucose in the bloodstream, we look at density (mmol/l or mg/dl for blood tests and mmol/mol or the old fashioned % for the HbA1C).

Maybe it means it can deal with 90grams of sugars/carbs you eat, maybe it means something else entirely.

 

[Deleted member 308541]

Empagliflozin is a selective inhibitor of SGLT2, providing dose-dependent UGE increases in healthy volunteers, with up to 90 g of glucose excreted per day.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079288/

Edit: Highlighted up to.

 

[LittleGreyCat]

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4079288/

You didn't highlight the "up to".

 

[Deleted member 308541]

You didn't highlight the "up to".

I was waiting for the OP to pick up on it.

I will do it now though....

 

[kokhongw]

Unless it removes more during high blood glucose period which is understandable if its removal is related to the blood glucose levels.

SGLT2i works by lowering the kidneys glucose reabsorption threshold. Eg normal kidney function will only start excreting glucose above 10 mmols, but by taking SGLT2i, glucose starts passing out around 7 mmols...so any glucose above 7 mmols will get passed out. Now you can have your cake and pee it...

 

[kokhongw]

For the downside, you may want to add Fournier's gangrene... pretty nasty stuff...

 

[Rabdos]

Does anyone know how much it curbs the postprandial curve?

 

[bulkbiker]

Does anyone know how much it curbs the postprandial curve?

It will depend on what the "prandial" was and everyone will be individual.

 

[kokhongw]

Does anyone know how much it curbs the postprandial curve?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904627/

I believe the first graph was wrongly labeled, and should indicate Plasma glucose and it shows a 2 mmol difference.

 

[kokhongw]

Other studies (rats/mices) that shows similar response curve... but its real magic is passing out the glucose and maintaining "time-in-range"... the latest measure of glycemic control success...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3980039/

 

[LittleGreyCat]

Less effective with kidney impairment, but doesn't say that it makes it worse.
I assume drinking more water helps to flush the kidneys.

 

[ringi]

I expect for most people it is better not to spend money buying the carbs, and hence forcing the NHS to spend money on a drug to put the carbs down the wc.

 

[Rose22]

Took this for a week...awful! I had to wee every 1/2 an hour, more you drink worse it is! I definitely did flush out loads of sugar! But the side effects simply outweighed any results, so after a grand total of 7 days had to stop.
It’s a great theory, get the excess sugar out the body...but until it’s not from kidney function and weeding it out, I’m steering clear.