4. Discussion
The present study examined whether a non-renal mechanism
contributes to the glucose lowering observed with canagliflozin
treatment in patients with type 2 diabetes. Patients with type 2
diabetes received 2 days of dosing of study drug – with the
second dose administered immediately before the standard
meal of a MMTT. Since canagliflozin 300 mg retains maximal
effects on UGE for 24 hours, no further UGE or UGE-associated
PG lowering was expected if an additional dose of canagliflozin
was administered just prior to the meal (Treatments C and D)
compared with when canagliflozin 300 mg was given the day
before (Treatment B). On the other hand, doses of canagliflozin
>200 mg administered prior to the morning meal have been
shown to provide greater reductions in glucose and insulin AUC
relative to lower doses, despite similar UGE [9], and a single dose
of canagliflozin 300 mg given just prior to a mixed meal in
healthy subjects delayed intestinal glucose absorption [12],
confirming that this dose of canagliflozin lowers postprandial
glucose through a non-renal mechanism.
In the present study in patients with type 2 diabetes,
canagliflozin 300 mg administered 24 hours prior to the
MMTT, without subsequent drug administration, effectively