Why does canagliflozin not work in female mice

#1

https://x.com/Aging_Scientist/status/1811812012365938833?s=19

#2

What does it imply if a compound works in female but not male mice, or vice versa?

#3

This was discussed in a podcast maybe 6 months or so ago(?), I think an Attia podcast but I’m not sure. Apparently the female mice had something like 30x the blood levels of canagliflozin compared to the males despite the same doses given. So speculation was that female mice absorb and/or metabolize cana differently than males, but more work needed to be done to figure out why, and if this also happens in other species including humans (and also if the higher blood levels was the actual cause of the lack of life extension effect in females).