Effect of Sitagliptin in Combination with Glimepiride on Glycemic Control and Islet Cell Diameter/Proliferation in A Model of Type 2 Diabetic Rats

The aim of the present study was to investigate the effect of monotherapy with sitagliptin, or its combination with glimepiride in glycemic control, islet cell diameter and its proliferation in type 2 diabetic rats. Rats were fed with a high fat diet followed by injection with a low dose of streptozotocin to induce type 2 diabetes. Then, rats were switched to normal diet and for other 28 days. Monotherapy with sitagliptin did not affect the body weight, while its combination with glimepiride did not induce a significant change. The combination increased the % change in body weight compared to sitagliptin alone. All the treatment regiment enhanced glucose clearance as indicated by a reduction in the area under the curve. Pancreatic immunohistochemistry and morphometric analysis were performed to measure the diameter of islet cells, insulin-positive area and the number of Ki-67 positive nuclei. In sitagliptin group, diameter of large-sized islets was 2-fold greater than those observed in diabetic group. The monotherapy with glimepiride did not change the islet-cell diameter. Further, the combination group showed better glycemic control and greater cell proliferation compared to monotherapies. Consequently, we conclude that the combination therapy of sitagliptin/glimepiride has synergistic effect.