Synergistic effect of α-glucosidase inhibitors and dipeptidyl peptidase 4 inhibitor treatment.
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).
Department of Diabetes and Endocrinology, Graduate School of Medicine, Gifu University, Gifu, Japan.
Yukio
Y
Horikawa
Department of Diabetes and Endocrinology, Graduate School of Medicine, Gifu University, Gifu, Japan.
Mayumi
M
Enya
Department of Diabetes and Endocrinology, Graduate School of Medicine, Gifu University, Gifu, Japan.
Katsumi
K
Iizuka
Department of Diabetes and Endocrinology, Graduate School of Medicine, Gifu University, Gifu, Japan.
Gui Ying
GY
Chen
Department of Diabetes and Endocrinology, Graduate School of Medicine, Gifu University, Gifu, Japan.
Shin-Ichi
S
Kawachi
Department of Diabetes and Endocrinology, Graduate School of Medicine, Gifu University, Gifu, Japan.
Tetsuya
T
Suwa
Department of Diabetes and Endocrinology, Graduate School of Medicine, Gifu University, Gifu, Japan.
Jun
J
Takeda
Glucagon‐like peptide‐1; Insulin; Postprandial hyperglycemia