Abstract: Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are one of the most frequently prescribed anti-diabetic agents in Japan, and they are often used in combination with insulin secretagogues, such as sulfonylureas and glinides. In the present study, we determined the efficacy and safety of the use of repaglinide or glimepiride, a sulfonylurea, in combination with a DPP-4I, in Japanese patients with type 2 diabetes mellitus (T2DM). This study was an investigator-initiated, open-label, randomized, multi-center prospective study. Patients with T2DM, which was inadequately controlled using a DPP-4I, were randomized to a repaglinide group or a glimepiride group and treated for 48 weeks. The primary outcomes were the reductions in glycated hemoglobin (HbA1c) and glucose oscillation, identified using continuous glucose monitoring, after 12 weeks. The secondary outcome was the change in carotid intima-media thickness (IMT), measured by ultrasonography, after 48 weeks. A total of 61 patients were recruited and analyzed in the study. Twelve weeks of treatment with 1.5 mg repaglinide or 1 mg glimepiride significantly reduced HbA1c, and a larger reduction in HbA1c occurred in the repaglinide group than the glimepiride group. Mean subcutaneous glucose concentration was significantly reduced in both groups, but the glucose oscillation did not decrease. Interestingly, the mean left IMT significantly increased in the glimepiride group, but not in the repaglinide group. More hypoglycemic events were observed in the glimepiride group. These data suggest that repaglinide reduces HbA1c more effectively than glimepiride when used in combination with a DPP-4I, and causes fewer hypoglycemic events.
Trail registry: This study is registered with UMIN-CTR (UMIN000018321).
Keywords: Atherosclerosis; Dipeptidyl peptidase-4 inhibitor; Glucose oscillation; Hypoglycemia; Insulin secretagogue.
© The Japan Diabetes Society 2020.