Sitagliptin versus mitiglinide switched from mealtime dosing of a rapid-acting insulin analog in patients with type 2 diabetes: a randomized, parallel-group study

PURPOSE: We determined the feasibility of substituting sitagliptin or mitiglinide for bolus insulin injection therapy in patients with type 2 diabetes. METHODS: 60 patients with type 2 diabetes were enrolled and randomized to switch from mealtime dosing of a rapid-acting insulin analog to either sitagliptin or mitiglinide for 16 weeks. RESULTS: Body weight, body mass index, and waist circumference decreased significantly in both groups at the end of the study. Mitiglinide significantly increased fasting plasma glucose (FPG) levels at the end of the study from 146.5±36.3 to 168.0±38.8 mg/dL, whereas sitagliptin did not affect FPG. Glycated hemoglobin (HbA1c) and 1,5-anhydroglucitol increased significantly in both groups. The C peptide immunoreactivity (CPR) responses after arginine were diminished in both groups. γ-GTP and triglycerides increased, and high-density lipoprotein cholesterol and adiponectin decreased, in the sitagliptin group, but not in the mitiglinide group. Mean Diabetes Treatment Satisfaction Questionnaire scores improved significantly in both groups. Patients whose mean total daily doses of rapid-acting insulin analog were 16.6 and 17.8 units were switched to sitagliptin and mitiglinide, respectively, without a change in the HbA1c level. Total insulin doses/body weight predicted changes in HbA1c only in the sitagliptin group, but not in the mitiglinide group. Use of >0.27 IU/kg of a rapid-acting insulin analog predicted an increase in HbA1c after switching to sitagliptin. The CPR index (CPI) was also a predictor for a change in HbA1c in the sitagliptin group, but not in the mitiglinide group; patients with a CPI<1.4 developed a worse HbA1c after switching to sitagliptin. CONCLUSIONS: Sitagliptin may predominantly act on FPG, whereas mitiglinide may act on postprandial plasma glucose to achieve glycemic control after switching from a bolus insulin regimen. Additional therapy to sitagliptin or mitiglinide is clearly required to obtain equivalent glycemic control in patients using a higher dose of insulin. TRIAL REGISTRATION NUMBER: (UMIN 000007051)