Effect of an Add-On SGLT2 Inhibitor on the Efficacy of DPP-4 Inhibitor Therapy in Improving Postprandial Hyperglycemia

Abstract

Objective: This study was conducted to investigate the effect of an add-on SGLT2 inhibitor on the efficacy of DPP-4 inhibitor therapy improving postprandial hyperglycemia in terms of its effect on diurnal glycemic variability (GV) to provide insight into the effect of the SGLT2 inhibitor on incretin-responsive insulin secretion. Patients and Methods: This study enrolled 12 type 2 diabetic patients with inadequate glycemic control despite treatment with the DPP-4 inhibitor teneligliptin (T) (20 mg/day) (Age, 69.5±7.4 years; BMI, 27.2±3.7 kg/m2; HbA1c, 7.7±0.7%). All patients were treated with add-on canagliflozin (Cana) 100 mg/day for 8 weeks and compared for diurnal GV before and after treatment with add-on Cana using CGM. Results: With the initiation of add-on Cana, a significant decrease was noted in body weight and BMI (P < 0.05). The HbA1c and GA values were significantly decreased (P < 0.05) and the adiponectin values significantly increased (P < 0.05). The diurnal GV indices, such as the SD of glucose values, total area between the 24-h mean glucose levels and glucose curve, and mean amplitude of glucose excursions (MAGE) significantly decreased (P < 0.05), as the pre-breakfast glucose values and the 24-hour mean glucose values significantly decreased with add-on Cana. Additionally, treatment with add-on Cana led to a significant decrease in the % of time in hyperglycemia but no significant change in the % of time in hypoglycemia. Conclusions: The mechanisms through which add-on Cana reduced diurnal GV in type 2 diabetic patients receiving T may be accounted for as follows: add-on Cana improved incretin-responsive insulin secretion through resolution of glucotoxicity resulting in enhancement of the efficacy of T in improving postprandial hyperglycemia, as well as weight loss through calorie loss via glycosuria, which, coupled with attendant improvements in insulin resistance, led to improvements in postprandial hyperglycemia and reductions in diurnal GV. Disclosure T. Onishi: None. Y. Taniguchi: None. Y. Mori: None.