α-Glucosidase inhibitors (αGIs) decrease plasma glucose and serum insulin levels in healthy subjects [1,2] and reduce the development of type 2 diabetes in subjects with impaired glucose tolerance (IGT) [3,4]. αGIs reportedly enhance active glucagon-like peptide-1 (GLP-1) responses and reduce total glucose-dependent insulinotropic polypeptide (GIP) responses [5][6][7]; however, their significance for protecting against the development of diabetes remains uncertain. Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as sitagliptin, increase active GLP-1 and GIP by inhibiting DPP-4 enzymatic activity and improve hyperglycemia in a glucose-dependent fashion by increasing serum insulin and decreasing serum glucagon levels in diabetic patients [8] abstract. α-glucosidase inhibitors (αGIs) increase active glucagon-like peptide-1 (GLP-1) and reduce the total glucosedependent insulinotropic polypeptide (GIP) levels, but their ability to prevent diabetes remains uncertain. Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as sitagliptin, increase active GLP-1 and GIP levels and improve hyperglycemia in a glucose-dependent fashion. However, the effectiveness of their combination in subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT) is uncertain. The present study evaluated the effect of miglitol, sitagliptin, and their combination on glucose, insulin and incretin levels in non-diabetic men. Miglitol and sitagliptin were administered according to four different intake schedules (C: no drug, M: miglitol; S: sitagliptin, M+S: miglitol and sitagliptin). The plasma glucose levels were significantly lower for M, S and M+S than for the control. The areas under the curve (AUCs) of the plasma active GLP-1 level in the M, S, and M+S groups were significantly greater than that in the control group. The AUC of the plasma active GLP-1 level was significantly greater for M+S group than for the M and S groups. The AUC of the plasma total GIP level was significantly smaller for M+S group than for the control and M and S groups. The results of our study suggest that miglitol, sitagliptin, or their combination contributes to the prevention of type 2 diabetes.

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.

Aims/Introduction:  One of the reasons for the poor adherence to α‐glucosidase inhibitor (αGI) treatment is the need to take medication three times a day. We hypothesized that the administration of miglitol might be effective for the next meal if the miglitol‐induced inhibition of α‐glucosidase activity persists until the next meal. In the present study, we evaluated whether the administration of miglitol just before or after breakfast was effective for postprandial glucose excursion after lunch without taking miglitol at lunch.Materials and Methods:  We measured the plasma glucose, serum insulin and glucagon, plasma active glucagon‐like peptide‐1 (GLP‐1), and total glucose‐dependent insulinotropic polypeptide levels in non‐diabetic men. Miglitol was given to each patient according to four different intake schedules (control: no drug; intake 1: drug given just before breakfast [50 mg]; intake 2: drug given 30 min after the start of breakfast [50 mg]; intake 3: drug given at the same time as intake 2, but without eating breakfast [50 mg]).Results:  Both intake 1 and intake 2 had a smaller area under the curve (AUC) for plasma glucose excursion after lunch, compared with the control. Intake 2 had a larger AUC for active GLP‐1 after lunch, compared with intake 1.Conclusions:  Intake 1 and intake 2 can improve postprandial hyperglycemia after lunch. The results of the present study raise the possibility that the administration of miglitol twice a day might be effective and might help to improve treatment adherence among diabetic patients. This trial was registered with UMIN Clinical Trial Registry (no. UMIN000002896). (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00129.x, 2011)

α-Glucosidase inhibitors (αGIs) decrease plasma glucose and serum insulin levels in healthy subjects [1,2] and reduce the development of type 2 diabetes in subjects with impaired glucose tolerance (IGT) [3,4]. αGIs reportedly enhance active glucagon-like peptide-1 (GLP-1) responses and reduce total glucosedependent insulinotropic polypeptide (GIP) responses [5][6][7][8]. Dipeptidyl peptidase-4 (DPP-4) inhibitors, such as sitagliptin or vildagliptin, increase active GLP-1 and GIP by inhibiting DPP-4 enzymatic activity and improve hyperglycemia in a glucose-dependent fashion by increasing serum insulin and decreasing serum glucagon levels in diabetic patients [9].Because miglitol and sitagliptin enhance plasmaEffects of miglitol, vildagliptin, or their combination on serum insulin and peptide YY levels and plasma glucose, cholecystokinin, ghrelin, and obestatin levels abstract. We previously reported that combination therapy with an α-glucosidase inhibitor (αGI) and a dipeptidyl peptidase-4 (DPP-4) inhibitor increased active glucagon-like peptide-1 (GLP-1) levels and decreased total glucose-dependent insulinotropic polypeptide (GIP) levels, compared with monotherapy, in non-diabetic men. However, the peptide YY (PYY), cholecystokinin (CCK), ghrelin, and obestatin levels in patients receiving a combination of αGIs and DPP-4 inhibitors have not been previously reported. We evaluated the effect of miglitol, vildagliptin, or their combination on these parameters. Miglitol and/or vildagliptin were administered according to four different intake schedules in eleven non-diabetic men (C: no drug, M: miglitol; V: vildagliptin, M+V: miglitol+vildagliptin). Blood samples were collected at 0, 30, 60, and 120 min after the start of breakfast. The plasma glucose, serum insulin, serum total PYY (PYY 1-36 and PYY 3-36 ), plasma CCK, plasma active ghrelin, and plasma obestatin levels were measured. The area under the curve (AUC) of the serum total PYY level in the M group was significantly greater than that in the C group, and the AUC of the serum total PYY level in the M+V group was significantly lower than that in the M group. The combination therapy did not change the AUC of the plasma CCK, plasma active ghrelin, plasma obestatin, and ghrelin/obestatin levels, compared with the control. The results of our study suggested that combination therapy with miglitol and vildagliptin had no effect on appetite regulation hormones, such as total PYY, CCK, active ghrelin, and obestatin, compared with the levels in the control group.

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