Effects of Sitagliptin on Pancreatic Beta-Cells in Type 2 Diabetes With Sulfonylurea Treatment: A Prospective Randomized Study

BACKGROUND: This prospective randomized, multicenter, open-label, comparative study was performed to analyze the effects of sitagliptin on glycemic control and maintenance of beta-cell function in patients with poorly controlled type 2 diabetes treated with low-dose glimepiride. METHODS: Forty-one patients with type 2 diabetes mellitus treated with low-dose glimepiride (≤ 2 mg/day) were prospectively enrolled in this study (age: 20 - 75 years; hemoglobin A1c (HbA1c): 7.4- 9.4%). The patients were randomized into two groups: the glimepiride (G) group, in which glimepiride dose was increased gradually to 6 mg/day, and the sitagliptin (S) group, in which sitagliptin was added at a dose of 50 mg/day. RESULTS: HbA1c level was significantly decreased after 24 weeks, but not 12 weeks, in the G group, while a significant decrease was seen after 12 weeks in the S group. Although there were no significant differences in HbA1c level at 24 weeks between the two groups (P = 0.057). The overall trend of changes in HbA1c level suggested that the glucose-lowering effects were superior in the S group. Furthermore, a significant change in fasting glucose was seen in the S group, but not in the G group. Glycemic control target was achieved in 36.7% and 16.7% patients in the S group and the G group, respectively. The proinsulin/insulin (P/I) ratio was significantly increased in the G group, whereas it tended to decrease in the S group. After 24 weeks of treatment, no significant difference was observed in the P/I ratio between the two groups, whereas a significant difference was noted in the ΔP/I (amount of change). Albuminuria tended to increase in the G group compared with the S group. CONCLUSION: The results of the present study suggested that sitagliptin effectively lowered hyperglycemia and that it may have a protective effect on pancreatic beta-cells when combined with a low dose of glimepiride. Therefore, sitagliptin may represent a useful combination therapy with low-dose sulfonylurea, not only for achieving glycemic control but also for protection of pancreatic beta-cells.