A NOVEL ANTIDIABETIC DRUG: MIGLITOL: A REVIEW

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About Authors:
Rahul kumar Singh
M.Pharm (Quality Assurance)
Sr. Officer Quality Assurance at Shreya Life Sciences Pvt. Ltd.,
Roorkee, Uttarakhand
rahulsingh.qa@gmail.com

Abstract
Miglitol, an oral alpha-glucosidase inhibitor, 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, miglitol 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. Because its mechanism of action is different, the effect of miglitol to enhance glycemic control is additive to that of sulfonylureas when used in combination. In addition, miglitol 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.

Miglitol inhibits glycoside hydrolase enzymes called alpha-glucosidases. Since miglitol works by preventing digestion of carbohydrates, it lowers the degree of postprandial hyperglycemia. It must be taken at the start of main meals to have maximal effect. Its effect will depend on the amount of non-monosaccharide carbohydrates in a person's diet.
In contrast to acarbose (another alpha-glucosidase inhibitor), miglitol is systemically absorbed; however, it is not metabolized and is excreted by the kidneys.

Reference Id: PHARMATUTOR-ART-1586

Introduction
Anti-diabetic drugs
treat diabetes mellitusby lowering glucose levels in the blood. With the exceptions of insulin, exenatide, and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors.

Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in Type I, which must be injected or inhaled.

Diabetes mellitus type 2 is a disease of insulin resistance by cells. Treatments include (1) agents which increase the amount of insulin secreted by the pancreas, (2) agents which increase the sensitivity of target organs to insulin, and (3) agents which decrease the rate at which glucose is absorbed from the gastrointestinal tract.

Classification –
1-Insulin

2- Secretagogues
·         2.1 Sulfonylureas
·         2.2 Meglitinides

3- Sensitizers
·         3.1 Biguanides
·         3.2 Thiazolidinediones

4- Alpha-glucosidase inhibitors

5- Peptide analogs
·         5.1 Incretin mimetics
·         5.1.1 Glucagon-like peptide (GLP) analogs and agonists
·         5.1.2 Gastric inhibitory peptide (GIP) analogs
·         5.2 DPP-4 inhibitors
·         5.3 Amylin analogues

6- Experimental agents

7- Herbal extracts
Alpha-glucosidase inhibitorsare oral anti-diabetic drugs used for diabetes mellitus type 2that work by preventing the digestion of carbohydrates (such as starchand table sugar). Carbohydrates are normally converted into simple sugars (monosaccharides) which can be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of carbohydrates on blood sugar.

Drugs used in alpha-glucosidase inhibitors:

  • Acarbose- Precose
  • Miglitol- Glyset
  • Voglibose

Even though the drugs have a similar mechanism of action, there are subtle differences between acarbose and miglitol. Acarbose is an oligosaccharide, whereas miglitol resembles a monosaccharide. Miglitol is fairly well-absorbed by the body, as opposed to acarbose. Moreover, acarbose inhibits pancreatic alpha-amylase in addition to alpha-glucosidase.

Clinical use
Alpha-glucosidase inhibitors are used to establish greater glycemic controlover hyperglycemia in diabetes mellitus type 2, particularly with regard to postprandial hyperglycemia. They may be used as monotherapy in conjunction with an appropriate diabetic diet and exercise, or they may be used in conjunction with other anti-diabetic drugs.

Alpha-glucosidase inhibitors may also be useful in patients with diabetes mellitus type 1; however, this use has not been officially approved by the Food and Drug Administration.

*Combination of miglitol, an anti-diabetic drug, and nicorandil markedly reduces myocardial infarct size through opening the mitochondrial KATP channels in rabbits.1
*Antidiabetic drug miglitol inhibits myocardial apoptosis involving decreased hydroxyl radical production and Bax expression in an ischaemia/reperfusion rabbit heart.2

*The α-glucosidase inhibitor miglitol suppresses postprandial hyperglycaemia and interleukin-1β and tumour necrosis factor-α gene expression in rat peripheral leucocytes induced by intermittent sucrose loading.

Mechanism of action
Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrates: specifically alpha-glucosidase enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidaseshydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine.

Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine.

Inhibition of these enzyme systems reduces the rate of digestion of carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels: the long term effect is a small reduction in haemoglobin.

In contrast to sulfonylureas, miglitol 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 miglitol to enhance glycemic control is additive to that of sulfonylureas when used in combination. In addition, miglitol 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.

Dosing
There is no fixed dosage regimen for the management of diabetes mellitus with miglitol any other pharmacologic agent. Dosage of miglitolmust be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended dosage of 100 mg 3 times daily. Miglitol should be taken three times daily at the start (with the first bite) of each main meal. miglitolshould 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 , one-hour postprandial plasma glucose may be used to determine the therapeutic response to miglitoland 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 miglitoleither as monotherapy or in combination with a sulfonylurea.

Since alpha-glucosidase inhibitors are competitive inhibitors of the digestive enzymes, they must be taken at the start of main meals to have maximal effect. Their effects on blood sugar levels following meals will depend on the amount of complex carbohydrates in the meal.

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