Oral therapy for type 1 diabetes mellitus using a novel immunomodulator, FTY720 (fingolimod), in combination with sitagliptin, a dipeptidyl peptidase-4 inhibitor, examined in non-obese diabetic mice.
Aims/Introduction:  The therapeutic effectiveness against type 1 diabetes mellitus of a novel immunomodulator, FTY720 (fingolimod), in combination with sitagliptin, a dipeptidyl peptidase-4 inhibitor, was examined in the non-obese diabetic (NOD) mouse model.


METHODS
Female NOD mice that had developed type 1 diabetes mellitus spontaneously were divided into four groups according to which therapy they received: (i) FTY720 (0.1 mg/kg, orally, six times a week) plus sitagliptin (1 mg/kg, orally, six times a week); (ii) FTY720 (0.1 mg/kg, orally, six times a week); (iii) sitagliptin (1 mg/kg, orally, six times a week); and (iv) the vehicle (water) alone. Therapeutic efficacy was evaluated in terms of survival rate, ratio of insulin-positive β-cells/total islet area, extent of islet inflammation (insulitis score) and blood-glucose level.


RESULTS
The therapeutic administration of FTY720 plus sitagliptin significantly improved survival (83% at 70 days after onset, P < 0.05) compared with sitagliptin alone (17%) or vehicle alone (0%). The fasting-blood glucose level, the ratio of insulin-positive β-cells/total islet area and the insulitis score in the surviving mice, which had been treated with FTY720 plus sitagliptin, were improved to the normal levels as in age-matched NOD mice with normoglycemia.


CONCLUSIONS
Combination therapy with FTY720 and sitagliptin is a promising candidate for type 1 diabetes mellitus treatment, and might allow the treatment of type 1 diabetes mellitus with only oral agents. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2012.00218.x, 2012).
Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka.
Takumi
T
Tsuji
Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka.
Yuya
Y
Yoshida
Research Institute for Production and Development, Kyoto, Japan.
Tetsuro
T
Fujita
Department of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka ; Research Institute for Production and Development, Kyoto, Japan.
Takeyuki
T
Kohno
FTY720; Non‐obese diabetic mouse; Type 1 diabetes mellitus