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. Materials and 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)