levels in combination with teneligliptin may add therapeutic
value in the control of glucose intolerance.
A number of SGLT2 inhibitors have been reported in non-clinical
and clinical studies. Among them, canagliflozin is an SGLT2 inhibitor
with moderate inhibitory activity for hSGLT1, which is unlike
other highly selective SGLT2 inhibitors (31). Thus, it is not certain
whether the synergistic effect on GLP-1 secretion with combined
treatment of a DPP4 inhibitor is shared with other highly selective
SGLT2 inhibitors. In addition to established treatments with SGLT2
inhibition and DPP4 inhibition in T2DM patients, treatment with a
combination of canagliflozin and a DPP4 inhibitor would be associated
with multiple antidiabetic effects of GLP-1 in the treatment
of T2DM.
Taken together, the combined treatment of canagliflozin and
teneligliptin improved glucose intolerance with similar insulin
release when compared to teneligliptin treatment alone. Combined
treatment also stimulated insulin release when compared to the
canagliflozin treatment alone. Although canagliflozin is an SGLT2
inhibitor, the combination effect is likely to be partly mediated by
its inhibitory action on intestinal SGLT1. Given the low incidence of
side effects of hypoglycemia, weight gain, and abdominal symptoms
with SGLT2 and DPP4 inhibitors (32,33), combined treatment
with canagliflozin and teneligliptin would be a good option for
treatment of T2DM.
Conflicts of interest
All the authors are employees of Mitsubishi Tanabe Pharma
Corporation.