Clinical study of repaglinide efficacy and safety in type 2 diabetes mellitus patients with blood glucose levels inadequately controlled by sitagliptin

Abstract

Aims/IntroductionThe aim of the present study was to evaluate the long‐term efficacy and safety of adding repaglinide in patients with type 2 diabetes mellitus whose blood glucose levels were not sufficiently controlled by treatment with a dipeptidyl peptidase‐4 inhibitor, sitagliptin, in addition to diet and exercise therapies.Materials and MethodsThis was a multicenter, uncontrolled, dose‐titration study with a treatment period of 52 weeks. The primary end‐point was the change in glycated hemoglobin levels from baseline.ResultsThe glycated hemoglobin level was 7.43 ± 0.57% (mean ± standard deviation) at baseline, and decreased to 6.93 ± 0.91% at the end of the study. The mean changes in glycated hemoglobin levels at 4 weeks and at the end of the study were −0.44 ± 0.28% and −0.50 ± 0.82%, respectively. The glycated hemoglobin‐lowering effect was maintained for 52 weeks. The rate of adverse events was 86.0% (86/100), and there were 352 adverse events. The rate of adverse drug reactions was 21.0% (21/100). Hypoglycemia was reported in 5.0% (5/100) of patients, but there was no incidence of ‘major hypoglycemia’.ConclusionsCombination therapy with repaglinide and sitagliptin was considered effective for a long term without clinical safety problems in patients with type 2 diabetes mellitus.

Efficacy and safety of repaglinide added to sitagliptin in Japanese patients with type 2 diabetes: A randomized 24-week open-label clinical trial

“…The mean change in fasting plasma glucose improved significantly in the ADD-ON group compared with the baseline and with the SWITCH group. These results were similar to the previous uncontrolled trial which added repaglinide to the treatment of Japanese patients with T2DM who were poorly controlled with sitagliptin [25]. In this regard, previous trials that examined the efficacy of repaglinide monotherapy [15] or the combination of repaglinide and metformin [17] showed greater HbA1c reduction rates (-1.57% and -1.28%, respectively).…”

“…Although both repaglinide and sitagliptin improve postprandial glucose excess when used alone or in combination with metformin [15,17,26,27], only a few clinical studies examined the postprandial effects of long-term combination therapy of DPP-4 inhibitor and glinides [24,25]. We reported previously a randomized controlled trial in which 24-week vildagliptin added to nateglinide in Japanese T2DM patients resulted in significant improvement in the AUC of glucose [24].…”

Antidiabetic and neuroprotective effects of a novel repaglinide analog

“…Following our results, many other experimental diabetic animal models stated that RPG or its analogs decrease blood sugar, primarily through stimulation of the pancreas, upregulation of postprandial insulin response, and an increase of its receptors' sensitivity. [39][40][41][42] In addition, several clinical trials assured that RPG treatment enhances glycemic control in type 2 DM patients while also favoring the parameters of oxidative stress (i.e., serum antioxidant capacity). [32,43,44] In the next step, we assessed whether OXR induces the genes involved in glucose metabolism and insulin secretion in pancreas islets.…”

Progress of the General Medicine Management Model in Patients with Type II Diabetes Mellitus

“…Currently, the treatment of type II diabetes mellitus is based on moderate exercise and dietary control in combination with two or more hypoglycaemic agents with different mechanisms of glucose-lowering action [9]. At present, drugs for the treatment of type II diabetes mellitus are clinically classified according to the mode of administration.…”