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

Abstract

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.

Usefulness of antidiabetic alpha-glucosidase inhibitors: a review on the timing of administration and effects on gut hormones

“…However, the exact effects of increased active GLP-1 after combination therapy in diabetes patients remain unknown; therefore, further research is needed to study this aspect. Subsequently, the effect of another combination therapy of an αGI and a DPP-4 inhibitor on gut hormones, such as total PYY (PYY 1-36 plus PYY ), CCK, ghrelin, and obestatin, were evaluated (Table 2) [36]. Miglitol and vildagliptin were administered to healthy men either as monotherapy or combination therapy, and the results were compared to those of the control group (no drug).…”

“…The authors suggested that these effects were due to the increased active GLP-1 levels and improved hyperglycemia by the combination therapy. Combination therapies of three different αGIs (acarbose, voglibose, or miglitol) and sitagliptin were administered to C57BL/6J mice [39], and all three combinations resulted in a synergic increase of Effects of miglitol, sitagliptin, or vildagliptin as monotherapy and combination therapy on postprandial gut hormones in healthy individuals [35,36]. Two arrows represent combination therapy: two upward arrows indicate that combination therapy increased the level of a specific variable compared with monotherapy, while two downward arrows indicate that combination therapy decreased the level of a specific variable compared with monotherapy.…”

Improved glucose regulation in type 2 diabetic patients with DPP-4 inhibitors: focus on alpha and beta cell function and lipid metabolism

“…An important effect of GLP-1 receptor agonists is a direct action on the brain stem to induce satiety and inhibit gastric emptying [59]. A variety of methods have been used to assess appetite and gastric emptying directly, including rate of ingested glucose into the circulation, surrogates of appetite such as ghrelin and gastrin levels or the paracetamol test of gastric emptying and findings indicate that DPP-4 inhibitors have no effect on satiety and gastric emptying [59,60,[91][92][93][94][95]. The prevailing evidence suggests that the effect of GLP-1 on satiety and gastric emptying requires doses of GLP-1 that are much higher than those achieved by DPP-4 inhibition [94].…”

Comparative Analysis of the Bonding Modes between Two Antidiabetic Drugs with beta-Glucosidases from Different Species

“…For example, H4 changed its position nearly 90°, which lead to three H-bonds interactions between H4, O4 and Gln45, Tyr452 and His148 (Table 4). Actually, multiple hydroxyl groups played a critical role in the stabilization of the miglitol at the catalytic sites of β-glucosidases [46][47][48][49] .…”