Side Effects of Glyset (miglitol)

Glyset (miglitol) is an alpha-glucosidase inhibitor used to control blood glucose (sugar) levels in type 2 diabetes. 

Carbohydrates that are eaten are digested by enzymes in the intestine into smaller sugars, which are absorbed into the body and raise blood sugar levels. The process of carbohydrate digestion requires the pancreas to release into the intestine alpha-amylase enzymes which digest the large carbohydrates into smaller carbohydrates called oligosaccharides. 

The cells lining the small intestine then release alpha-glucosidase enzymes that further digest the oligosaccharides into single sugars, like glucose, that can be absorbed. 

Glyset is a man-made oligosaccharide designed to slow down the actions of alpha-amylase and alpha-glucosidase enzymes thereby slowing the appearance of sugar in the blood after a meal (postprandial hyperglycemia). It does not increase insulin production, and its effect on glucose is additive to the effect from other types of drugs used to treat type 2 diabetes. 

Glyset may reduce the weight gain that frequently is caused by sulfonylureas, another type of drug used to treat type 2 diabetes. 

Common side effects of Glyset include

• abdominal pain,
• diarrhea, and
• gas (flatulence).

Rare side effects of Glyset include

• low serum iron and
• skin rash.

Drug interactions of Glyset include digoxin, because Glyset may interfere with digoxin absorption thereby decreasing digoxin blood levels and its effect. Glyset also may reduce the effectiveness of ranitidine and propranolol.

• Intestinal adsorbents (for example, charcoal) and digestive enzymes (for example, amylase, pancreatin) may reduce the effect of Glyset and should not be taken concomitantly.
• Adding a sulfonylurea during therapy with Glyset may lower blood glucose further, and the risk for developing low blood sugar (hypoglycemia) is greater.
• If mild to moderate hypoglycemia occurs while taking Glyset in combination with a sulfonylurea, oral glucose (dextrose) should be used for treatment instead of sucrose (table sugar).
• Since Glyset blocks the digestion of sucrose to glucose, hypoglycemia will not be rapidly corrected if sucrose is given. Glyset alone does not produce hypoglycemia. 

There are no safety and efficacy studies of Glyset use during pregnancy in humans. Insulin therapy is recommended during pregnancy. 

Glyset is excreted in human breast milk in small amounts. Drug exposure to the infant is expected although in small amounts. Glyset is not recommended for breastfeeding mothers.

The most common side effects of miglitol are:

• abdominal pain,
• diarrhea, and
• flatulence.

Rare but possible side effects include:

• low serum iron, and
• skin rash.

Gastrointestinal

Gastrointestinal symptoms are the most common reactions to Glyset Tablets. In U.S. placebocontrolled trials, the incidences of abdominal pain, diarrhea, and flatulence were 11.7%, 28.7%, and 41.5% respectively in 962 patients treated with Glyset 25 100 mg 3 times daily, whereas the corresponding incidences were 4.7%, 10.0%, and 12.0% in 603 placebo-treated patients. The incidence of diarrhea and abdominal pain tended to diminish with continued treatment.

Dermatologic

Skin rash was reported in 4.3% of patients treated with Glyset compared to 2.4% of placebo-treated patients. Rashes were generally transient and most were assessed as unrelated to Glyset by physician investigators.

Abnormal Laboratory Findings

Low serum iron occurred more often in patients treated with Glyset (9.2%) than in placebo-treated patients (4.2%) but did not persist in the majority of cases and was not associated with reductions in hemoglobin or changes in other hematologic indices.

Postmarketing Experience

The following adverse reactions have been reported during post-approval use of Glyset. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Gastrointestinal Disorders: ileus (including paralytic ileus), subileus, gastrointestinal pain, nausea, abdominal distention.

Pneumatosis Cystoides Intestinalis

There have been rare postmarketing reports of pneumatosis cystoides intestinalis associated with the use of alpha-glucosidase inhibitors, including Glyset. Pneumatosis cystoides intestinalis may present with symptoms of

• diarrhea,
• mucus discharge,
• rectal bleeding, and
• constipation.

Complications may include

• pneumoperitoneum,
• volvulus,
• intestinal obstruction,
• intussusception,
• intestinal hemorrhage, and
• intestinal perforation.

If pneumatosis cystoides intestinalis is suspected, discontinue Glyset and perform the appropriate diagnostic imaging.

• Miglitol may interfere with digoxin (Lanoxin) absorption thereby decreasing digoxin blood levels and its effect. Therefore, the digoxin dose may need to be increased if miglitol is begun.
• Miglitol also may reduce the effectiveness of ranitidine (Zantac) and propranolol (Inderal). An adjustment in dose based on monitoring of the patient may be necessary if miglitol is used with either of these drugs.
• Intestinal adsorbents (for example, charcoal) and digestive enzymes (for example, amylase, pancreatin) may reduce the effect of miglitol and should not be taken concomitantly.
• Adding a sulfonylurea during therapy with miglitol may lower blood glucose further, and the risk for developing hypoglycemia is greater. Caution should be used when combining these drugs.
• If mild to moderate hypoglycemia occurs while taking miglitol in combination with a sulfonylurea, oral glucose (dextrose) should be used for treatment instead of sucrose (table sugar). Since miglitol blocks the digestion of sucrose to glucose, hypoglycemia will not be rapidly corrected if sucrose is given. Miglitol alone does not produce hypoglycemia.
• 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 for 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. 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 for 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 study with healthy volunteers, 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 for 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 carbohydratesplitting 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.