Synergistic effect of α-glucosidase inhibitors and dipeptidyl peptidase 4 inhibitor treatment

Abstract

Monotherapy of α‐glucosidase inhibitor (α‐GI) or dipeptidyl peptidase 4 (DPP4) inhibitor does not sufficiently minimize glucose fluctuations in the diabetic state. In the present study, we evaluated the combined effects of various of α‐GI inhibitors (acarbose, voglibose or miglitol) and sitagliptin, a DPP4 inhibitor, on blood glucose fluctuation, insulin and active glucagon‐like peptide‐1 (GLP‐1) levels after nutriment loading in mice. Miglitol and sitagliptin elicited a 47% reduction (P < 0.05) of the area under the curve of blood glucose levels for up to 2 h after maltose‐loading, a 60% reduction (P < 0.05) in the range of blood glucose fluctuation, and a 32% decrease in plasma insulin compared with the control group. All three of the combinations elicited a 2.5–4.9‐fold synergistic increase in active GLP‐1 (P < 0.05 vs control). Thus, combined treatment with the α‐GI miglitol, which more strongly inhibits the early phase of postprandial hyperglycemia, and DPP4 inhibitor yields both complementary and synergistic effects, and might represent a superior anti‐hyperglycemic therapy. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00081.x, 2011)

Effect of race on the glycaemic response to sitagliptin: Insights from the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS)

“…As 1 of the effects of acarbose is to increase incretin release, and given the consequent potential for synergy with DPP‐4i, we assessed whether there was any evidence of such an interaction in the Asian TECOS participants. Although the uptake of acarbose during the trial was proportionally greatest in the 2 Asian groups, there was no significant multiplicative effect of the combination on HbA1c levels.…”

“…To assess potential racial differences in the longer‐term effects of sitagliptin, we also examined the likelihood for Asians and other races to require additional glucose‐lowering therapies once open‐label therapies (other than DPP‐4i or GLP‐1 receptor analogues) were permitted from 4 months onwards. As acarbose may be more effective in Asians than other races in managing T2D, and given that there is preclinical evidence of synergy between acarbose and sitagliptin, we also examined whether this therapeutic combination was more effective in Asian TECOS participants.…”

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

“…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.…”

Acarbose, lente carbohydrate, and prebiotics promote metabolic health and longevity by stimulating intestinal production of GLP-1

“…The up-regulatory impact of any of these measures on GLP-1 levels should be considerably potentiated by concurrent administration of dipeptidyl peptidase 4 (DPP4) inhibitors—for example, sitagliptin, vildagliptin—which slow the proteolytic degradation of GLP-1 in plasma. 111 …”