Miglitol administered before breakfast increased plasma active glucagon-like peptide-1 (GLP-1) levels after lunch in patients with type 2 diabetes treated with sitagliptin

Abstract

We recently reported that the administration of miglitol alone just before breakfast improved postprandial hyperglycemia and increased active glucagon-like peptide-1 (GLP-1) levels after lunch in men without diabetes. Miglitol and dipeptidyl peptidase-4 inhibitors, such as sitagliptin, enhance plasma active GLP-1 concentrations via different mechanisms; therefore, combined therapy with these agents was more effective than monotherapy. In this study, we compared the effectiveness of the administration of miglitol alone just before breakfast on the plasma glucose, serum insulin and glucagon, and plasma incretin levels in sitagliptin-treated patients with type 2 diabetes. We measured the plasma glucose, serum insulin and glucagon, plasma active GLP-1, and total glucose-dependent insulinotropic polypeptide levels before breakfast, at 120 min after breakfast, before lunch, and 60 and 120 min after lunch in patients with diabetes who are receiving sitagliptin. This trial was performed for the following 2 days on each subject (Day 1: no miglitol, Day 2: miglitol alone [50 mg] administered just before breakfast). The area under the curve (AUC) of the plasma glucose levels after lunch in the miglitol-treated group tended to be lower than that in the miglitol-untreated group, but the difference was not statistically significant. Miglitol alone administered at breakfast increased the AUC of the active plasma GLP-1 levels after lunch in sitagliptin-treated patients with diabetes. Our results suggest that the once-daily administration of miglitol as a "GLP-1 enhancer" in combination with sitagliptin was effective for the treatment for patients with diabetes.

Effects of miglitol, vildagliptin, or their combination on serum insulin and peptide YY levels and plasma glucose, cholecystokinin, ghrelin, and obestatin levels

“…The effects of miglitol, vildagliptin, and their combination on plasma glucose and serum insulin were consistent with our previous report [10,11]. The absence of an increase in serum insulin levels in the V and M+V groups might be favorable for sparing insulin secretion by β cells in individuals with NGT.…”

“…By contrast, the administration of miglitol alone increased the AUC of the total PYY level. Based on the results of the present study, the combination therapy did not appear to have any effect on intestinal appetite regulation hormones, such as total PYY, CCK, active ghrelin, and obestatin, unlike the previously reported additive increase in active GLP-1 levels [10,11].…”

“…We hypothesized that combination therapy with the drugs used in this study would increase the active GLP-1 levels and decrease the total GIP levels, compared with monotherapy, based on our previous results [10,11]. Therefore, with regard to the hormones that are secreted by the intestine in response to the administration of αGIs and DPP-4 inhibitors, the changes in GLP-1 and GIP were expected to favor body weight reduction or the suppression of appetite.…”

“…Combination therapy using these drugs increased the active GLP-1 levels and decreased the total GIP levels, compared with monotherapy, in nondiabetic men [10]. Interestingly, the administration of miglitol only at breakfast increased the AUC of the active plasma GLP-1 levels from breakfast to 2 hours after the start of lunch in sitagliptin-treated Japanese patients with type 2 diabetes [11].…”

Efficacy of adding once- and thrice-daily voglibose in Japanese type 2 diabetic patients treated with alogliptin

“…In addition, it is also suggested that although the agents are usually administered thrice a day, only a once-daily administration might have some efficacy on glycemic control [33]. However, all of these studies were performed for only a several days.…”