Acarbose is a complex oligosaccharide that delays the digestion of ingested carbohydrates, thereby resulting in a smaller rise in blood glucose concentration following meals. As a consequence of plasma glucose reduction, PRECOSE® reduces levels of glycosylated hemoglobin in patients with type 2 diabetes mellitus. Systemic non-enzymatic protein glycosylation, as reflected by levels of glycosylated hemoglobin, is a function of average blood glucose concentration over time.

Mechanism of Action: In contrast to sulfonylureas, PRECOSE® does not enhance insulin secretion. The antihyperglycemic action of acarbose results from a competitive, reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolase enzymes. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, while the membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in a delayed glucose absorption and a lowering of postprandial hyperglycemia.

Because its mechanism of action is different, the effect of PRECOSE® to enhance glycemic control is additive to that of sulfonylureas, insulin or metformin when used in combination. In addition, PRECOSE® diminishes the insulinotropic and weight-increasing effects of sulfonylureas.

Acarbose has no inhibitory activity against lactase and consequently would not be expected to induce lactose intolerance.

Pharmacokinetics

Absorption: In a study of 6 healthy men, less than 2% of an oral dose of acarbose was absorbed as active drug, while approximately 35% of total radioactivity from a ¹⁴C-labeled oral dose was absorbed. An average of 51% of an oral dose was excreted in the feces as unabsorbed drug-related radioactivity within 96 hours of ingestion. Because acarbose acts locally within the gastrointestinal tract, this low systemic bioavailability of parent compound is therapeutically desired. Following oral dosing of healthy volunteers with ¹⁴C-labeled acarbose, peak plasma concentrations of radioactivity were attained 14-24 hours after dosing, while peak plasma concentrations of active drug were attained at approximately 1 hour. The delayed absorption of acarbose-related radioactivity reflects the absorption of metabolites that may be formed by either intestinal bacteria or intestinal enzymatic hydrolysis.

Metabolism: Acarbose is metabolized exclusively within the gastrointestinal tract, principally by intestinal bacteria, but also by digestive enzymes. A fraction of these metabolites (approximately 34% of the dose) was absorbed and subsequently excreted in the urine. At least 13 metabolites have been separated chromatographically from urine specimens. The major metabolites have been identified as 4-methylpyrogallol derivatives (i.e., sulfate, methyl, and glucuronide conjugates). One metabolite (formed by cleavage of a glucose molecule from acarbose) also has alpha-glucosidase inhibitory activity. This metabolite, together with the parent compound, recovered from the urine, accounts for less than 2% of the total administered dose.

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