Antidiabetic effects of SGLT2 inhibitor ipragliflozin in type 2 diabetic mice fed diets containing different carbohydrate contents

Aims: Daily intake of carbohydrates differs among individual patients with type 2 diabetes. Here, we investigated whether or not dietary carbohydrate content affects the efficacy of the sodium-glucose cotransporter 2 (SGLT2) inhibitor ipragliflozin in type 2 diabetic mice. Main methods: Diabetic mice were fed a regular (50% kcal), high (75% kcal)-, or low (25% kcal)-carbohydrate diet. Ipragliflozin was orally administered once a day for 4 weeks. Key findings: In all groups, mice exhibited characteristics of type 2 diabetes, including hyperglycemia, hyperinsulinemia, and obesity. Hyperglycemia was more severe in the high-carbohydrate diet group and milder in the low-carbohydrate diet group than in the regular diet group. In all diabetic mice, ipragliflozin significantly increased urinary glucose excretion and improved hyperglycemia, hyperinsulinemia, glucose tolerance, insulin resistance, obesity, and nephropathy. Although these antidiabetic effects of ipragliflozin were more marked in the high-carbohydrate diet group (which showed more severe hyperglycemia) than in the other two groups, no significant differences in effective dose or degree of response were observed among the three groups. Significance: The antidiabetic effects of ipragliflozin were not greatly affected by dietary carbohydrate content, suggesting that ipragliflozin may have similar efficacy for patients with type 2 diabetes regardless of carbohydrate intake.