Glyset Information
Glyset ()
Glyset () Description
Glyset () Tablets contain miglitol, an oral alpha-glucosidase inhibitor for use in the management of non-insulin-dependent diabetes mellitus (NIDDM). Miglitol is a desoxynojirimycin derivative, and is chemically known as 3,4,5-piperidinetriol, 1-(2-hydroxyethyl)-2-(hydroxymethyl)-, [2R-(2α,3β,4α, 5β)]-. It is a white to pale-yellow powder with a molecular weight of 207.2. Miglitol is soluble in water and has a pK of 5.9. Its empirical formula is CHNO and its chemical structure is as follows:
Glyset () is available as 25 mg, 50 mg and 100 mg tablets for oral use. The inactive ingredients are starch, microcrystalline cellulose, magnesium stearate, hypromellose, polyethylene glycol, titanium dioxide, and polysorbate 80.
Glyset () Clinical Pharmacology
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 α-glucoside hydrolase enzymes. Membrane-bound intestinal α-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.
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.
Glyset () Clinical Studies
Glyset () Tablets were evaluated in two U.S. and three non-U.S. controlled, fixed-dose, monotherapy studies, in which 735 patients treated with Glyset () were evaluated for efficacy analyses (see ).
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 patients treated with Glyset () 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.
Study 3 was a 6-month dose-ranging trial evaluating Glyset () at doses from 25 mg 3 times daily to 200 mg 3 times daily. Glyset () produced a greater reduction in HbA1c than placebo at all doses, although the effect was statistically significant only at the 100 mg 3 times daily and 200 mg 3 times daily doses. In addition, all doses of Glyset () produced significant reductions in postprandial plasma glucose and postprandial insulin levels compared to placebo.
Studies 4 and 5 were 6-month studies evaluating Glyset () at 50 and 100 mg 3 times daily, and 100 mg 3 times daily, respectively. As compared to placebo, Glyset () produced significant reductions in HbA1c, as well as a significant reduction in postprandial plasma glucose in both studies at the doses employed.
Glyset () was studied as adjunctive therapy to a background of maximal or near-maximal sulfonylurea (SFU) treatment in three large, double-blind, randomized studies (two U.S. and one non-U.S.) in which 471 patients treated with Glyset () were evaluated for efficacy (see ).
Study 6 included patients under treatment with maximal doses of SFU at entry. At the end of this 14-week study, the mean treatment effects on glycosylated hemoglobin (HbA1c) were -0.82% and -0.74% for patients receiving Glyset () 50 mg 3 times daily plus SFU, and Glyset () 100 mg 3 times daily plus SFU, respectively.
Study 7 was a one-year study in which Glyset () at 25, 50 or 100 mg 3 times daily was added to a maximal dose of glyburide (10 mg twice daily). At the end of this study, the mean treatment effects on HbA1c of Glyset () when added to maximum glyburide therapy were -0.30%, -0.62%, and -0.73% with the 25, 50 and 100 mg 3 times daily dosages of Glyset () , respectively.
In Study 8, the addition of Glyset () 100 mg 3 times daily to a background of treatment with glyburide produced an additional mean treatment effect on HbA1c of -0.66%.
Results from controlled, fixed-dose studies of Glyset () as monotherapy or as combination treatment with a sulfonylurea were combined to derive a pooled estimate of the difference from placebo in the mean change from baseline in glycosylated hemoglobin (HbA1c) and postprandial plasma glucose as shown in Figures 1 and 2:
Because of its mechanism of action, the primary pharmacologic effect of miglitol is manifested as a reduction in postprandial plasma glucose, as shown previously in all of the major clinical trials. Glyset () was statistically significantly different from placebo at all doses in each of the individual studies with respect to effect on mean one-hour postprandial plasma glucose, and there is a dose response from 25 to 100 mg 3 times daily for this efficacy parameter.
Glyset () Indications And Usage
Glyset () is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Glyset () Contraindications
Glyset () Tablets are contraindicated in patients with:
Glyset () Precautions
Several studies investigated the possible interaction between miglitol and glyburide. In six healthy volunteers given a single dose of 5-mg glyburide on a background of 6 days treatment with miglitol (50 mg 3 times daily for 4 days followed by 100 mg 3 times daily for 2 days) or placebo, the mean C and AUC values for glyburide were 17% and 25% lower, respectively, when glyburide was given with miglitol. In a study in diabetic patients in which the effects of adding miglitol 100 mg 3 times daily × 7 days or placebo to a background regimen of 3.5 mg glyburide daily were investigated, the mean AUC value for glyburide was 18% lower in the group treated with miglitol, although this difference was not statistically significant. Further information on a potential interaction with glyburide was obtained from one of the large U.S. clinical trials (Study 7) in which patients were dosed with either miglitol or placebo on a background of glyburide 10 mg twice daily. At the 6-month and 1-year clinic visits, patients taking concomitant miglitol 100 mg 3 times daily exhibited mean C values for glyburide that were 16% and 8% lower, respectively, compared to patients taking glyburide alone. However, these differences were not statistically significant. Thus, although there was a trend toward lower AUC and C values for glyburide when co-administered with Glyset () , no definitive statement regarding a potential interaction can be made based on the foregoing three studies.
The effect of miglitol (100 mg 3 times daily × 7 days) on the pharmacokinetics of a single 1000-mg dose of metformin was investigated in healthy volunteers. Mean AUC and C values for metformin were 12% to 13% lower when the volunteers were given miglitol as compared with placebo, but this difference was not statistically significant.
In a healthy volunteer study, co-administration of either 50 mg or 100 mg miglitol 3 times daily together with digoxin reduced the average plasma concentrations of digoxin by 19% and 28%, respectively. However, in diabetic patients under treatment with digoxin, plasma digoxin concentrations were not altered by co-administration of miglitol 100 mg 3 times daily × 14 days.
Other healthy volunteer studies have demonstrated that miglitol may significantly reduce the bioavailability of ranitidine and propranolol by 60% and 40%, respectively. No effect of miglitol was observed on the pharmacokinetics or pharmacodynamics of either warfarin or nifedipine.
Intestinal adsorbents (e.g., charcoal) and digestive enzyme preparations containing carbohydrate-splitting enzymes (e.g., amylase, pancreatin) may reduce the effect of Glyset () and should not be taken concomitantly.
In 12 healthy males, concomitantly administered antacid did not influence the pharmacokinetics of miglitol.
Miglitol was administered to mice by the dietary route at doses as high as approximately 500 mg/kg body weight (corresponding to greater than 5 times the exposure in humans based on AUC) for 21 months. In a two-year rat study, miglitol was administered in the diet at exposures comparable to the maximum human exposures based on AUC. There was no evidence of carcinogenicity resulting from dietary treatment with miglitol.
A combined male and female fertility study conducted in Wistar rats treated orally with miglitol at dose levels of 300 mg/kg body weight (approximately 8 times the maximum human exposure based on body surface area) produced no untoward effect on reproductive performance or capability to reproduce. In addition, survival, growth, development, and fertility of the offspring were not compromised.
Glyset () Overdosage
Unlike sulfonylureas or insulin, an overdose of Glyset () Tablets will not result in hypoglycemia. An overdose may result in transient increases in flatulence, diarrhea, and abdominal discomfort. Because of the lack of extra-intestinal effects seen with Glyset () , no serious systemic reactions are expected in the event of an overdose.
Glyset () Dosage And Administration
There is no fixed dosage regimen for the management of diabetes mellitus with Glyset () Tablets or any other pharmacologic agent. 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 (with the first bite) of each main meal. Glyset () should be started at 25 mg, and the dosage gradually increased as described below, 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 (see ), 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 three 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.
Glyset () How Supplied
Glyset () Tablets are available as 25 mg, 50 mg, and 100 mg white, round, film-coated tablets. The tablets are debossed with the word "Glyset () " on one side and the strength on the other side, as indicated below.
Glyset ()
Glyset () Principal Display Panel - Mg Tablet Bottle Label
Glyset () Principal Display Panel - Mg Tablet Bottle Label
Glyset () Principal Display Panel - Mg Tablet Bottle Label
