General Information

Glyset (miglitol) is an oral alpha-glucosidase inhibitor.

Glyset is specifically indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Glyset is supplied as tablets for oral adminiistration.

There is no fixed dosage regimen for the management of diabetes mellitus with Glyset Tablets. Dosage of Glyset must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dosage of 100 mg 3 times daily. Glyset should be taken three times daily at the start of each main meal. Glyset should be started at 25 mg, and the dosage gradually increased both to reduce gastrointestinal adverse effects and to permit identification of the minimum dose required for adequate glycemic control of the patient.

During treatment initiation and dose titration one-hour postprandial plasma glucose may be used to determine the therapeutic response to Glyset and identify the minimum effective dose for the patient. Thereafter, glycosylated hemoglobin should be measured at intervals of approximately 3 months. The therapeutic goal should be to decrease both postprandial plasma glucose and glycosylated hemoglobin levels to normal or near normal by using the lowest effective dose of GLYSET, either as monotherapy or in combination with a sulfonylurea.

Initial Dosage

The recommended starting dosage of Glyset is 25 mg, given orally three times daily at the start of each main meal. However, some patients may benefit by starting at 25 mg once daily to minimize gastrointestinal adverse effects, and gradually increasing the frequency of administration to 3 times daily.

Maintenance Dosage

The usual maintenance dose of Glyset is 50 mg taken 3 times daily, although some patients may benefit from increasing the dose to 100 mg 3 times daily. To allow adaptation to potential gastrointestinal adverse effects, it is recommended that Glyset therapy be initiated at a dosage of 25 mg 3 times daily, then gradually titrated upward to allow adaptation. After 4 to 8 weeks of the 25 mg 3 times daily regimen, the dosage should be increased to 50 mg 3 times daily for approximately three months, following which a glycosylated hemoglobin level should be measured to assess therapeutic response. If at that time, the glycosylated hemoglobin level is not satisfactory, the dosage may be further increased to 100 mg 3 times daily, the maximum recommended dosage.

Mechanism of Action

Miglitol 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, GLYSET Tablets 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. In contrast to sulfonylureas, GLYSET does not enhance insulin secretion. The antihyperglycemic action of miglitol results from a reversible inhibition of 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 poptprandial hyperglycemia.

Because its mechanism of action is different, the effect of Glyset to enhance glycemic control is additive to that of sulfonylureas when used in combination. In addition, GLYSET 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.

Clinical Trial Results

Two large studies undertaken by Bayer have shown that Glyset is particularly effective among Hispanic and African-American Type II patients. This is significant because Type II diabetes is more prevalent and is more commonly associated with complications in these subpopulations compared to Caucasian Type II patients.

Hispanics have a 300 percent higher chance of developing Type II diabetes than the general population and African-Americans are 60 percent more likely to develop Type II diabetes than Caucasians. Hispanic and African-American Type II patients have been typically under-represented in clinical trials of new diabetes therapies. The demonstration of Glyset’s efficacy and safety in these sub-populations confirm its importance as a therapeutic option for these patients.

In study 1, a one-year study in which Glyset was evaluated as monotherapy and also as combination therapy, there was a statistically significantly smaller increase in mean glycosylated hemoglobin (HbA1c) over time in the miglitol 50 mg 3 times daily monotherapy arm compared to placebo. Significant reductions in mean fasting and postprandial plasma glucose levels and in mean postprandial insulin levels were observed in Glyset-treated patients compared with the placebo group.

In study 2, a 14-week study, there was a significant decrease in HbA1c in patients receiving Glyset 50 mg 3 times daily or 100 mg 3 times daily compared to placebo. In addition, there were significant reductions in postprandial plasma glucose and postprandial serum insulin levels compared to placebo.