| Indication |
For use as an adjunct to diet to improve glycemic control in
patients with non-insulin-dependent diabetes mellitus (NIDDM) whose
hyperglycemia cannot be managed with diet alone. |
| Pharmacodynamics |
Miglitol, an oral alpha-glucosidase inhibitor, is a
desoxynojirimycin derivative 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, miglitol reduce levels of glycosylated hemoglobin in patients
with Type II (non-insulin-dependent) diabetes mellitus. Systemic
nonenzymatic protein glycosylation, as reflected by levels of
glycosylated hemoglobin, is a function of average blood glucose
concentration over time. Because its mechanism of action is different,
the effect of miglitol to enhance glycemic control is additive to that
of sulfonylureas when used in combination. In addition, miglitol
diminishes the insulinotropic and weight-increasing effects of
sulfonylureas. Miglitol has minor inhibitory activity against lactase
and consequently, at the recommended doses, would not be expected to
induce lactose intolerance. |
| Mechanism of action |
In contrast to sulfonylureas, miglitol does not enhance insulin
secretion. The antihyperglycemic action of miglitol results from a
reversible inhibition of membrane-bound intestinal a-glucoside hydrolase
enzymes. Membrane-bound intestinal a-glucosidases hydrolyze
oligosaccharides and disaccharides to glucose and other monosaccharides
in the brush border of the small intestine. In diabetic patients, this
enzyme inhibition results in delayed glucose absorption and lowering of
postprandial hyperglycemia. |
| Absorption |
Absorption of miglitol is saturable at high doses with 25 mg being
completely absorbed while a 100-mg dose is only 50-70% absorbed. No
evidence exists to show that systemic absorption of miglitol adds to its
therapeutic effect. |
| Volume of distribution |
|
| Protein binding |
The protein binding of miglitol is negligible (<4.0%). |
| Metabolism |
Miglitol is not metabolized in man or in any animal species studied. |
| Route of elimination |
Miglitol is not metabolized in man or in any animal species studied. It is eliminated by renal excretion as an unchanged drug. |
| Half life |
The elimination half-life of miglitol from plasma is approximately 2 hours. |
| Clearance |
Not Available |
| Toxicity |
Unlike sulfonylureas or insulin, an overdose will not result in
hypoglycemia. An overdose may result in transient increases in
flatulence, diarrhea, and abdomi-nal discomfort. Because of the lack of
extra-intestinal effects seen with miglitol, no serious systemic
reactions are expected in the event of an overdose. |
