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).

Keywords: Glucagon‐like peptide‐1; Insulin; Postprandial hyperglycemia.

Figure 1

Blood glucose profiles after oral administration of α‐glucosidase inhibitor (α‐GI) and sitagliptin (0.3 mg/kg) in maltose‐loaded normal mice. (a) Acarbose, 10 mg/kg; (b) voglibose, 0.1 mg/kg; (c) miglitol, 3 mg/kg. Each value represents mean ± SD of 8–10 mice. *P < 0.05, **P < 0.01, ***P < 0.001 vs the control group using to Dunnett’s multiple comparison test.