Acute and short term effects of intestinal alpha-glucosidase inhibition on gut hormone responses in man

The effect of 50-, 100-, 200-, and 400-mg oral doses of acarbose, a competitive inhibitor of intestinal α-glucosidases, on the postprandial release of gut and pancreatic hormones after a 2.2 MJ carbohydrate-rich mixed test meal was determined in five normal subjects according to a double-blind, Latin-square protocol. All the doses of acarbose tested slowed the postprandial plasma glucose rise, without evidence of dose dependency, while maximal inhibition of integrated insulin and gastric inhibitory polypeptide responses to 31 ±8% and 28±7% of control values, respectively, was obtained at the 400-mg dose. The enteroglucagon response was increased to a maximum of 905±262% of control at the 200-mg dose, and total motilin responses were slightly but not significantly elevated. After one week of regular acarbose administration at 100 mg three times daily, the effects of the 100-mg dose on insulin and enteroglucagon responses were slightly enhanced, and there was no evidence of intestinal adaptation in the form of diminished postprandial endocrine responses. The observed effects are attributed to impairment of carbohydrate digestion in the upper small intestine and suggest that the optimal ratio of desired to unwanted effects is obtained at low doses of acarbose.