Effects of mitiglinide, a short-acting insulin secretagogue, on daily glycemic variability and oxidative stress markers in japanese patients with type 2 diabetes mellitus

Background and Objective: The objective of this study was to clarify the effects of mitiglinide on daily glycemic variability and oxidative stress markers in outpatients with type 2 diabetes mellitus that is insufficiently controlled by diet and/or non-insulin secretagogues. Methods: We enrolled 24 patients with type 2 diabetes whose glycemic control had been suboptimal [i.e. glycosylated hemoglobin (HbA_1c) ≥6.9 %]. The patients were treated with mitiglinide 10 mg three times daily for 16 weeks. If their glycemic control was not improved at week 8, the dose of mitiglinide was increased to 20 mg three times daily. Daily glycemic variability was assessed by 7-point self-monitoring of blood glucose for 2 days, and standard deviation (SD), M value, and mean of daily differences (MODD) were calculated. Oxidative stress was assessed by oxidized low-density lipoprotein, pentosidine, urinary 8-iso-prostaglandin F2alpha, and urinary 8-hydroxydeoxy guanosine. Results: After 16 weeks of mitiglinide treatment, the HbA_1c level was significantly decreased (mean ± SD, 7.4 ± 0.7 to 6.8 ± 0.5 %, P < 0.0001). Postprandial glucose excursion and glycemic variability were also significantly improved after mitiglinide treatment (all P < 0.05). The reductions in SD, M value, and MODD were 17, 50, and 48 %, respectively. There was a significant positive correlation between the change in HbA_1c and change in SD during the study (r = 0.454, P = 0.03). There were no significant changes in oxidative stress markers. Conclusions: The present study supports the notion that mitiglinide improves postprandial glucose excursion and HbA_1c level in patients with type 2 diabetes. In addition, we demonstrated that mitiglinide also effectively improves daily glycemic variability. The effect of mitiglinide on oxidative stress needs further investigation.