ABSTRACT
The effect of 50-, 100-, 200-, and 400-mg oral doses of acarbose, a competitive inhibitor of intestinal alpha-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.
Subject(s)
Gastrointestinal Hormones/metabolism , Glycoside Hydrolase Inhibitors , Pancreatic Hormones/metabolism , Trisaccharides/administration & dosage , Acarbose , Adaptation, Physiological , Adult , Blood Glucose/analysis , Dietary Carbohydrates/metabolism , Dose-Response Relationship, Drug , Double-Blind Method , Female , Glucagon-Like Peptides/metabolism , Humans , Insulin Antagonists/metabolism , Intestinal Absorption/drug effects , Male , Motilin/metabolism , Tablets , Time Factors , Trisaccharides/pharmacologyABSTRACT
Seventeen non-insulin-dependent diabetics poorly controlled by diet and sulphonylurea drugs took part in a long-term (20-52 weeks) trial of the effect of an alpha-glucosidase inhibitor (acarbose 100 mg thrice daily) on postprandial glycaemic and gastro-entero-pancreatic hormone responses. Patients were assessed before, during, and after the trial period with identical 2.2 MJ mixed test meals plus placebo or acarbose 100 mg, and sulphonylurea therapy was continued throughout. Acarbose administration reduced the integrated postprandial plasma responses of glucose to 58 +/- 10% (mean +/- SEM, p less than 0.001), insulin to 61 +/- 10% (p less than 0.01) and gastric inhibitory polypeptide to 45 +/- 8% (p less than 0.001) of control values, increased the enteroglucagon response to 152 +/- 26% (p less than 0.001) of control and slightly prolonged the postprandial release of motilin. Recorded glycosuria was significantly (p less than 0.01) reduced throughout the treatment period. The effects of acarbose on postprandial glycaemic and endocrine responses remained approximately constant throughout the trial period, and responses returned to pre-treatment values within 2 days of stopping treatment.
