Switching Dipeptidyl Peptidase-4 Inhibitors to Tofogliflozin, a Selective Inhibitor of Sodium-Glucose Cotransporter 2 Improve Arterial Stiffness Evaluated by Cardio-Ankle Vascular Index in Patients with Type 2 Diabetes: A Pilot Study

Background: We have found that anagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4) significantly ameliorates arterial stiffness in Type 2 Diabetes Mellitus (T2DM) patients compared with an equivalent hypoglycaemic agent, glimepiride. However, it remains unclear whether switching DPP-4 inhibitors to tofogliflozin, a selective inhibitor of Sodium-Glucose Cotransporter 2 (SGLT2) improves arterial stiffness in T2DM patients. Methods: Nineteen T2DM patients who had received DPP-4 inhibitors for at least 1 year were enrolled in this study. Clinical parameters and arterial stiffness evaluated by cardio-ankle vascular index (CAVI) were measured at baseline and after 6-months treatment with tofogliflozin. Results: At 6 months after switching to tofogliflozin, CAVI, waist circumference, body weight, body mass index, subcutaneous and visceral fat volume, white blood cell number, fasting plasma insulin, uric acid, aspartate transaminase (AST), gamma-glutamyl transferase (GTP), and advanced glycation end products (AGEs) were significantly reduced, while red blood cell number, haemoglobin, and HbA(1c) values were increased. When stratified by median values of change in CAVI after switching to tofogliflozin (Delta CAVI), baseline serum levels of AGEs were significantly higher in the low Delta CAVI group (high responder) than in the high one (low responder). Delta AST and Delta GTP were positively correlated with Delta CAVI. Conclusion: The present study suggests that switching DPP-4 inhibitors to tofogliflozin ameliorates arterial stiffness in T2DM patients partly via improvement of liver function. Baseline serum levels of AGEs may identify patients who improve arterial stiffness more after treatment with tofogliflozin.