Recommended Topic Related To:

Glyset

"Nov. 27, 2012 -- Countries that mix high-fructose corn syrup into processed foods and soft drinks have higher rates of diabetes than countries that don't use the sweetener, a new study shows.

In a study published in the journal Glo"...

Glyset

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-insulindependent) diabetes mellitus. Systemic nonenzymatic 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, 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 αglucosidases 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.

Pharmacokinetics

Absorption

Absorption of miglitol is saturable at high doses: a dose of 25 mg is completely absorbed, whereas a dose of 100 mg is 50% - 70% absorbed. For all doses, peak concentrations are reached in 2 to 3 hours. There is no evidence that systemic absorption of miglitol contributes to its therapeutic effect.

Distribution

The protein binding of miglitol is negligible ( < 4.0%). Miglitol has a volume of distribution of 0.18 L/kg, consistent with distribution primarily into the extracellular fluid.

Metabolism

Miglitol is not metabolized in humans or in any animal species studied. No metabolites have been detected in plasma, urine or feces, indicating a lack of either systemic or pre-systemic metabolism.

Excretion

Miglitol is eliminated by renal excretion as unchanged drug. Following a 25 mg dose, over 95% of the dose is recovered in the urine within 24 hours. At higher doses, the cumulative recovery of drug from urine is somewhat lower due to the incomplete bioavailability. The elimination half-life of miglitol from plasma is approximately 2 hours.

Special Populations

Renal Impairment

Because miglitol is excreted primarily by the kidneys, accumulation of miglitol is expected in patients with renal impairment. Patients with creatinine clearance < 25 mL/min taking 25 mg 3 times daily, exhibited a greater than two-fold increase in miglitol plasma levels as compared to subjects with creatinine clearance > 60 mL/min. Dosage adjustment to correct the increased plasma concentrations is not feasible because miglitol acts locally. Little information is available on the safety of miglitol in patients with creatinine clearance < 25 mL/min. Therefore, treatment of these patients with miglitol is not recommended.

Hepatic impairment

Miglitol pharmacokinetics were not altered in cirrhotic patients relative to healthy control subjects. Since miglitol is not metabolized, no influence of hepatic function on the kinetics of miglitol is expected.

Gender

No significant difference in the pharmacokinetics of miglitol was observed between elderly men and women when body weight was considered.

Race

Several pharmacokinetic studies were conducted in Japanese volunteers, with results similar to those observed in Caucasians. A study comparing the pharmacodynamic response to a single 50 mg dose in Black and Caucasian healthy volunteers indicated similar glucose and insulin responses in both populations.

Clinical Studies

Clinical Experience in Non-Insulin-Dependent Diabetes Mellitus (NIDDM) Patients on Dietary Treatment Only

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 Table 1).

In Study 1, a 1-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 at the 100 mg 3 times daily and 200 mg 3 times daily. 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 reductions in HbA1c, as well as a significant reduction in postprandial plasma glucose in both studies at the doses employed.

Table 1 : Results of Monotherapy Study with GLYSET

Study Treatment HbA1c (%) 1-hour Postprandial Glucose (mg/dL)
Mean Change from Baseline* Treatment Effect** Mean Change from Baseline Treatment Effect**
1 (U.S.) Placebo +0.71 +24
GLYSET 50 mg 3 times daily +0.13 -0.58† -39 -63†
2 (U.S.) Placebo +0.47 +15
GLYSET 50 mg 3 times daily -0.22 -0.69† -52 -67†
GLYSET 100 mg 3 times daily -0.28 -0.75† -59 -74†
3 (non-U.S.) Placebo +0.18 +2
GLYSET 25 mg 3 times daily -0.08 -0.26 -33 -35†
GLYSET 50 mg 3 times daily -0.22 -0.40 -45 -47†
GLYSET 100 mg 3 times daily -0.63 -0.81† -62 -64†
GLYSET 200 mg 3 times daily‡ -0.84 -1.02† -85 -87†
4 (non-U.S.) Placebo +0.01 +8
GLYSET 50 mg 3 times daily -0.35 -0.36† -20 -28†
GLYSET 100 mg 3 times daily -0.57 -0.58† -25 -33†
5 (non-U.S.) Placebo +0.32 +17
GLYSET 100 mg 3 times daily -0.43 -0.75† -38 -55†
* Mean baseline ranged from 7.54 to 8.72% in these studies.
** The result of subtracting the placebo group average.
† p ≤ 0.05
‡ Although results for the 200 mg 3 times daily are presented for completeness, the maximum recommended dosage of GLYSET is 100 mg 3 times daily.

Clinical Experience in NIDDM Patients Receiving Sulfonylureas

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 Table 2).

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 1-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 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%.

Table 2 : Results of Combination Therapy with GLYSET Plus Sulfonylurea (SFU)

Study Treatment HbA1c
(%)
1-hour Postprandial Glucose (mg/dL)
Mean Change from Baseline* Treatment Effect** Mean Change from Baseline Treatment Effect**
6 (U.S.) Placebo + SFU +0.33 --- -1 ---
GLYSET 50 mg 3 times daily + SFU -0.49 -0.82† -69 -68†
GLYSET 100 mg 3 times daily + SFU -0.41 -0.74† -73 -72†
7 (U.S.) Placebo + SFU +1.01 --- 48 ---
GLYSET 25 mg 3 times daily+ SFU +0.71 -0.30 -2 -50†
GLYSET 50 mg 3 times daily+ SFU +0.39 -0.62† -13 -61†
GLYSET 100 mg 3 times daily+ SFU +0.28 -0.73† -33 -81†
8 (non-U.S.) Placebo + SFU +0.16 --- +10 ---
GLYSET 100 mg 3 times daily+ SFU -0.50 -0.66† -36 -46†
* Mean baseline ranged from 8.56 to 9.16% in these studies.
** The result of subtracting the placebo group average.
† p ≤ 0.05

Figure 1 : HbAc (%) Mean Change From Baseline: Treatment Effect Pooled Results from Controlled Fixed-Dose Studies in Tables 1 and 2

HbAc (%) Mean Change From Baseline -  Illustration

Figure 2 : 1-Hour Postprandial Plasma Glucose Mean Change From Baseline: Treatment Effect Pooled Results from Controlled Fixed-Dose Studies in Table 1 and 2

Plasma Glucose Mean Change From Baseline - Illustration

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.

Last reviewed on RxList: 10/2/2012
This monograph has been modified to include the generic and brand name in many instances.

A A A

Glyset - User Reviews

Glyset User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Glyset sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Women's Health

Find out what women really need.

advertisement
advertisement
Use Pill Finder Find it Now See Interactions

Pill Identifier on RxList

  • quick, easy,
    pill identification

Find a Local Pharmacy

  • including 24 hour, pharmacies

Interaction Checker

  • Check potential drug interactions
Search the Medical Dictionary for Health Definitions & Medical Abbreviations