Antidiabetic Drugs

Posts Tagged ‘Glyset’

(British Approved Name, US Adopted Name, rINN)

Drug Nomenclature

International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish):

Adverse Effects and Precautions

As for alpha-glucosidase inhibitors in general (see Acarbose). Skin rash may occur. Miglitol should be used with caution in patients with renal impairment.

Interactions

As for alpha-glucosidase inhibitors in general (see Acarbose). Miglitol may reduce the bioavailability of propranolol and ranitidine.

Pharmacokinetics

Miglitol is completely absorbed at a dose of 25 mg, but only 50 to 70% is absorbed at a dose of 100 mg. It is not metabolised, and is excreted unchanged in the urine with a plasma elimination half-life of about 2 hours.

Uses and Administration

Miglitol is an alpha-glucosidase inhibitor similar in action to acarbose. It is given orally in the management of type 2 diabetes mellitus, alone or with a sulfonylurea. Usual initial doses are 25 mg three times daily with meals, increased if necessary to a maximum of 100 mg three times daily.

Proprietary Preparations

Austria: Diastabol

Czech Republic: Diastabol

France: Diastabol

Germany: Diastabol

Hungary: Diastabol

India: Diamig Mignar †

Mexico: Diastabol

Poland: Diastabol

Portugal: Diastabol Limarcan

Spain: Diastabol Plumarol

Sweden: Diastabol

Switzerland: Diastabol

USA: Glyset

Alpha-glucosidase inhibitors also were popular in Europe prior to their introduction into the American market. At this time, they remain one of the most frequendy prescribed antidiabetic agents in Europe. Acarbose was the first agent in this class widely available in the United States. Alpha-glucosidase inhibitors act by blocking the absorption of carbohydrate from the gastrointestinal tract and are most effective in decreasing postprandial glucose elevation. The main advantage of these agents is that they act locally in the gut and are not systemic in their activity. Due to their nonsystemic activity, hypoglycemia is not associated with alpha-glucosidase inhibitors. The disadvantages, however, are greater in number.

Acarbose

Brand Name Drug: in Europe under the brand name Glucobay, in North America as Precose, and in Canada as Prandase

Acarbose and the other agents of this class have relatively weak antidiabetic activity, only reducing HgbA₁C by .5%-1% in most patients. Diarrhea and flatulence are the most common side effects, occurring in up to 40% of patients in most trials. Secondary to the high incidence of gastrointestinal distress, acarbose should be initiated slowly. It comes in 50-mg and 100-mg tablets, and it is currendy recommended that patients begin with 25 mg daily taken with a meal. Afterward, it can be advanced to 25 mg with two meals and slowly increased to a maximum of 300 mg/day. Acarbose should be taken with the first bite of the meal and the most benefit is achieved with doses > 150 mg/day. It is at these higher dosages that a recent study has shown reduction of HgbA₁C of 1%-2%. Unfortunately, the incidence of gastrointestinal side effects often precludes reaching these doses.

Miglitol

Brand Name Drug: Glyset

Recendy, miglitol, a new alpha-glucosidase inhibitor, was approved by the Food and Drug Administration. It reportedly has many of the gastrointestinal side effects that limit acarbose use. However, in preliminary studies, miglitol effectively lowered postprandial blood glucose and glycosylated hemoglobin levels.

Brand Name: Glyset
Active Ingredient: miglitol
Approved uses: Glyset is indicated as monotherapy for the treatment of non-insulin dependent diabetes mellitus as an adjunct to diet to improve glycemic control in patients whose hyperglycemia can not be controlled by diet alone. Glyset is also approved for combination therapy with a sulfonylurea.
Company Name: Pharmacia & Upjohn Inc.
Availability: Prescription only

Glyset: Introduction

Glyset (miglitol) is an oral alpha-glucosidase inhibitor that is similar to acarbose (Precose®). Glyset has not yet demonstrated hepatotoxicity, which has occurred with the use of Precose. Although Glyset was first approved by the FDA in 1996, Pharmacia & Upjohn recently acquired the rights to Glyset and launched its sale in the US.

Glyset: How It Works

Glyset is a reversible inhibitor of membrane-bound intestinal alpha-glucoside hydrolase enzymes. These enzymes hydrolyze oligosaccharides and disaccharides to glucose and other monosaccharides in the small intestine. In patients with diabetes, inhibition of this enzyme results in delayed glucose absorption and lowering of postprandial hyperglycemia. Glyset can be used in combination with sulfonylureas to enhance glycemic control.

Glyset: Clinical Study Results

Several controlled, fixed-dose studies have been conducted to demonstrate the efficacy of Glyset monotherapy. The first study was one year in duration and evaluated a combination of Glyset and a sulfonylurea, in addition to Glyset as monotherapy. The results indicated that there was a statistically smaller increase in mean glycosylated hemoglobin (HbA1c) over time in the Glyset 50 mg three times a day arm when compared to placebo. Mean fasting and postprandial plasma glucose levels as well as mean postprandial insulin levels were significantly reduced in the Glyset group in comparison to the placebo group. In a 14-week study, patients in the Glyset group had a significant decrease in HbA1c in comparison to those taking placebo. The dose of Glyset used in this study was either 50 mg 0or 100 mg three times a day. Significant decreases in postprandial plasma glucose levels and postprandial insulin levels were seen in the Glyset group.

Several studies have also examined the use of Glyset in combination with sulfonylureas. The first study was 14 weeks’ duration and enrolled patients already on maximal doses of sulfonylureas. The patients received either Glyset 50 mg or 100 mg three times a day or placebo. Patients in the Glyset group had significantly reduced HbA1c levels at the end of the study period. A second study enrolled patients on maximum doses of glyburide and added either Glyset 25 mg, 50 mg or 100 mg three times a day or placebo to the regimen. At the end of the study, patients in both of the Glyset groups had significantly reduced HbA1c levels.

Glyset: What The Patient Should Know

Glyset is contraindicated in patients with diabetic ketoacidosis, inflammatory bowel disease, colonic ulceration or partial intestinal obstruction, and in patients predisposed to intestinal obstruction. Glyset should also be avoided in patients who suffer from chronic intestinal diseases associated with marked disorders of digestion or absorption, or those with conditions that may deteriorate as a result of increased gas formation in the intestine.

Glyset should be taken three times a day at the start of each main meal with the first bite of food.

Glyset does not cause hypoglycemia when administered alone, even in the fasted state. However, sulfonylureas and insulin can lower blood sugar levels enough to cause hypoglycemia. When Glyset is given in combination with a sulfonylurea or insulin it may increase the hypoglycemic potential of these agents. It is important that the patient and other family members recognize and understand the symptoms, predisposing factors, and treatment of hypoglycemia. Because Glyset prevents the breakdown of table sugar, a source of glucose should be kept available to be administered if the patient is taking Glyset in addition to sulfonylureas and insulin.

The most common adverse effects of Glyset are primarily dose-related gastrointestinal effects including flatulence, soft stools, diarrhea, or abdominal discomfort. Side effects, if they occur, usually develop in the first few weeks of therapy and generally diminish in frequency and intensity with time.