Do mixed sglt2 inhibitors synergize with each other

#1

Eg is halving the dose of canagliflozin and empagliflozin more effective than one pure strategy effective dose of each

[their activity is not EXACTLY identical]

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#2

Do they have different mechanisms of action?

#3

yes, one is a sglt1 inhibitor and the second is an sglt2 inhibitor

#4

Canagliflozin is also an SGLT2 inhibitor.

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#5

Both of these are SGLT2 inhibitors.

#6

I think Alex is interested in finding out if adding some of the SGLT1 inhibition from canagliflozin will complement a pure SGLT2I such as empagliflozin, or is it just best to stick to one or the other.

I’d hazard a guess that most of the benefits come from SGLT2I, and I don’t really need the SGLT1I.

#7

That is a bold guess…

… since the only ITP or other actual longevity studies and data are all with Cana / SGLT1, there are mechanistic reasons to think the gut effects (which you don’t get from just 2-inhibition) are important for longevity, and it’s only for SGLT1 that we have Mendelian Randomization data for mortality.

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#8

True. I could be wrong. However I do like the results for empagliflozin, so I’m going to give that a try first. As more data is available, it may change my mind.

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#9

My understanding is that cana inhibites both 1 and 2

#10

Totally. Anything I said make it sound like I think otherwise?