Primary Pharmacologic Effect of Alpha-Glucosidase Inhibitors
Alpha-glucosidase inhibitors work by delaying the breakdown of complex carbohydrates and absorption of glucose in the upper small intestine. 1, 2
Mechanism of Action
Alpha-glucosidase inhibitors competitively inhibit alpha-glucosidase enzymes located in the brush border of the small intestine, which are responsible for cleaving oligosaccharides into absorbable monosaccharides 1, 3
By blocking these enzymes, the drugs delay the digestion of complex carbohydrates (starch and sucrose) into glucose, thereby slowing glucose absorption and reducing postprandial hyperglycemia 4, 5
The carbohydrates are not prevented from absorption entirely—they are simply absorbed more distally in the gastrointestinal tract, which explains why malabsorption and weight loss do not occur 1
This mechanism results in increased delivery of undigested carbohydrates to the colon, where bacterial fermentation produces gas, explaining the characteristic gastrointestinal side effects (flatulence, bloating) seen in 25-45% of patients 1, 2
What Alpha-Glucosidase Inhibitors Do NOT Do
They do not augment glucose-dependent insulin secretion—this is the mechanism of incretin-based therapies (GLP-1 agonists and DPP-4 inhibitors), not alpha-glucosidase inhibitors 4
They do not reduce hepatic glucose production—this is the primary mechanism of metformin and thiazolidinediones 4
They do not regulate genes involved in glucose metabolism—this is the mechanism of thiazolidinediones (PPAR-γ activators) 4
Clinical Implications of the Mechanism
Because alpha-glucosidase inhibitors act locally in the gastrointestinal tract and do not stimulate insulin secretion or affect insulin action directly, they carry virtually no risk of hypoglycemia when used as monotherapy 1, 2
The primary pharmacologic effect manifests as a reduction in postprandial plasma glucose by 40-50 mg/dL, with a more modest effect on fasting glucose 5, 3
When hypoglycemia occurs in patients taking alpha-glucosidase inhibitors with insulin or sulfonylureas, it must be treated with glucose or honey—not complex carbohydrates or sucrose—because the drug blocks the breakdown of these substances 1, 6