eg-Acarbose(brand name-Precose)
eg-Miglitol(brand name-Glyset)
activity-Slow the digestion of sugar
Description
PRECOSE® (acarbose tablets) is an oral alpha-glucosidase inhibitor for use in the management of type 2 diabetes mellitus. Acarbose is an oligosaccharide which is obtained from fermentation processes of a microorganism, Actinoplanes utahensis, and is chemically known as O-4,6-dideoxy- 4-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-2-cyclohexen-1-yl]amino]- α-D-glucopyranosyl-(1 → 4)-O-α-D-glucopyranosyl-(1 → 4)-D-glucose. It is a white to off-white powder with a molecular weight of 645.6. Acarbose is soluble in water and has a pKa of 5.1. Its empirical formula is C25H43NO18
dosage
PRECOSE® is available as 25 mg, 50 mg and 100 mg tablets for oral use. The inactive ingredients are starch, microcrystalline cellulose, magnesium stearate, and colloidal silicon dioxide.
Clinical Pharmacology
Acarbose is a complex oligosaccharide 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, PRECOSE® reduces levels of glycosylated hemoglobin in patients with type 2 diabetes mellitus. Systemic non-enzymatic 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, PRECOSE® does not enhance insulin secretion. The antihyperglycemic action of acarbose results from a competitive, reversible inhibition of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolase enzymes. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine, while the membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine. In diabetic patients, this enzyme inhibition results in a delayed glucose absorption and a lowering of postprandial hyperglycemia.
Because its mechanism of action is different, the effect of PRECOSE® to enhance glycemic control is additive to that of sulfonylureas, insulin or metformin when used in combination. In addition, PRECOSE® diminishes the insulinotropic and weight-increasing effects of sulfonylureas.
Acarbose has no inhibitory activity against lactase and consequently would not be expected to induce lactose intolerance.
Contraindications
PRECOSE® is contraindicated in patients with known hypersensitivity to the drug and in patients with diabetic ketoacidosis or cirrhosis. PRECOSE® is also contraindicated in patients with inflammatory bowel disease, colonic ulceration, partial intestinal obstruction or in patients predisposed to intestinal obstruction. In addition, PRECOSE® is contraindicated in patients who have chronic intestinal diseases associated with marked disorders of digestion or absorption and in patients who have conditions that may deteriorate as a result of increased gas formation in the intestine.
Adverse Reactions
Digestive Tract: Gastrointestinal symptoms are the most common reactions to PRECOSE®. In U.S. placebo-controlled trials, the incidences of abdominal pain, diarrhea, and flatulence were 19%, 31%, and 74% respectively in 1255 patients treated with PRECOSE® 50-300 mg t.i.d., whereas the corresponding incidences were 9%, 12%, and 29% in 999 placebo-treated patients. In a one-year safety study, during which patients kept diaries of gastrointestinal symptoms, abdominal pain and diarrhea tended to return to pretreatment levels over time, and the frequency and intensity of flatulence tended to abate with time. The increased gastrointestinal tract symptoms in patients treated with PRECOSE® are a manifestation of the mechanism of action of PRECOSE® and are related to the presence of undigested carbohydrate in the lower GI tract.
If the prescribed diet is not observed, the intestinal side effects may be intensified. If strongly distressing symptoms develop in spite of adherence to the diabetic diet prescribed, the doctor must be consulted and the dose temporarily or permanently reduced.
Elevated Serum Transaminase Levels: See
Other Abnormal Laboratory Findings: Small reductions in hematocrit occurred more often in PRECOSE®-treated patients than in placebo-treated patients but were not associated with reductions in hemoglobin. Low serum calcium and low plasma vitamin B6 levels were associated with PRECOSE® therapy but are thought to be either spurious or of no clinical significance.
Glyset (miglitol)
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 pKa of 5.9. Its empirical formula is C8H17NO5
dosage
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.
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.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 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.
Indications And Usage
GLYSET Tablets, as monotherapy, are indicated as an adjunct to diet to improve glycemic control in patients with non-insulin-dependent diabetes mellitus (NIDDM) whose hyperglycemia cannot be managed with diet alone. GLYSET may also be used in combination with a sulfonylurea when diet plus either GLYSET or a sulfonylurea alone do not result in adequate glycemic control. The effect of GLYSET to enhance glycemic control is additive to that of sulfonylureas when used in combination, presumably because its mechanism of action is different.
In initiating treatment for NIDDM, diet should be emphasized as the primary form of treatment. Caloric restriction and weight loss are essential in the obese diabetic patient. Proper dietary management alone may be effective in controlling blood glucose and symptoms of hyperglycemia. The importance of regular physical activity when appropriate should also be stressed. If this treatment program fails to result in adequate glycemic control, the use of GLYSET should be considered. The use of GLYSET must be viewed by both the physician and patient as a treatment in addition to diet and not as a substitute for diet or as a convenient mechanism for avoiding dietary restraint.
Contraindications
GLYSET Tablets are contraindicated in patients with:
Diabetic ketoacidosis
Inflammatory bowel disease, colonic ulceration, or partial intestinal obstruction, and in patients predisposed to intestinal obstruction
Chronic intestinal diseases associated with marked disorders of digestion or absorption, or with conditions that may deteriorate as a result of increased gas formation in the intestine
Hypersensitivity to the drug or any of its components.
Adverse Reactions
Gastrointestinal:Gastrointestinal symptoms are the most common reactions to GLYSET Tablets. In U.S. placebo-controlled 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 considerably 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.
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