Add-on Treatment with Mitiglinide Improves Residual Postprandial Hyperglycemia in Type 2 Diabetic Patients Receiving the Combination Therapy with Insulin Glargine and Sitagliptin

The combination of a dipeptidyl peptidase-4 (DPP-4) inhibitor and a long-acting insulin analogue is widely used in clinical practice. However, some patients fail to achieve lower postprandial hyperglycemia. Mitiglinide, a short-acting insulinotropic sulfonylurea receptor ligand, is effective for postprandial hyperglycemia. Recently, it has been reported that the combination therapy of mitiglinide with a DPP-4 inhibitor could improve glycemic control. However, the efficacy of those under long-acting insulin analogue therapy remains to be investigated. Thus, we conducted a prospective single-center study of eight Japanese patients with type 2 diabetes mellitus receiving mitiglinide added to the combination therapy of sitagliptin and insulin glargine, and evaluated its efficacy and safety by continuous glucose monitoring (CGM). Participants' (four men and four women) mean age was 70.3 +/- 10.6 years. Their mean body mass index, HbA1c level, and urinary C-peptide level were 22.0 +/- 2.8 kg/m(2), 9.2 +/- 1.2%, and 50.0 +/- 31.4 mu g/day, respectively. CGM showed that as compared with the combination of only sitagliptin and insulin glargine, mitiglinide in combination with sitagliptin and insulin glargine significantly reduced glycennic fluctuation indices, total area for the range of 24-h glycemic fluctuations (p = 0.04), mean amplitude of glycemic excursions (p = 0.03), and the proportion of time in hyperglycemia (p = 0.02) without significant difference in the proportion of time in hypoglycemia (p = 0.18). Hence, we have demonstrated the efficacy and safety of the add-on treatment with mitiglinide in type 2 diabetic patients, receiving the combination therapy of sitagliptin and insulin glargine.