DESCRIPTION
Voglibose -Voglibose (INN and USAN) is an alpha-glucosidase inhibitor used for lowering post-prandial blood glucose levels in people with diabetes mellitus. It is made in India by Ranbaxy Labs and sold under the trade name Volix.Metformin-Metformin is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus (NIDDM). It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin-mediated glucose uptake. Metformin is the only oral antihyperglycemic agent that is not associated with weight gain. Metformin may induce weight loss and is the drug of choice for obese NIDDM patients. When used alone, metformin does not cause hypoglycemia; however, it may potentiate the hypoglycemic effects of sulfonylureas and insulin. Its main side effects are dyspepsia, nausea and diarrhea. Dose titration and/or use of smaller divided doses may decrease side effects. Metformin should be avoided in those with severely compromised renal function (creatinine clearance < 30 ml/min), acute/decompensated heart failure, severe liver disease and for 48 hours after the use of iodinated contrast dyes due to the risk of lactic acidosis. Lower doses should be used in the elderly and those with decreased renal function. Metformin decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Metformin may also have a positive effect on lipid levels. In 2012, a combination tablet of linagliptin plus metformin hydrochloride was marketed under the name Jentadueto for use in patients when treatment with both linagliptin and metformin is appropriate.Glimpride -Glimepiride is the first III generation sulphonyl urea it is a very potent sulphonyl urea with long duration of action.
CATEGORIES
Voglibose -Antidiabetic Agents.Metformin-Antidiabetic Agents.Glimpride -Hypoglycemic Agents, Immunosuppressive Agents, Anti-Arrhythmia Agents, Antidiabetic Agent.
CHEMICAL FORMULA
Voglibose -C10H21NO7.Metformin-C4H11N5.Glimpride -C24H34N4O5S.
COMPOSITION
Voglibose 0.2mg + Glimepiride 2mg + Metformin 500mg
INDICATION
Voglibose -For the treatment of diabetes. It is specifically used for lowering post-prandial blood glucose levels thereby reducing the risk of macrovascular complications.Metformin-For use as an adjunct to diet and exercise in adult patients (18 years and older) with NIDDM. May also be used for the management of metabolic and reproductive abnormalities associated with polycystic ovary syndrome (PCOS). Jentadueto is for the treatment of patients when both linagliptin and metformin is appropriate. Glimpride -For concomitant use with insulin for the treatment of noninsulin-dependent (type 2) diabetes mellitus.
PHARMACODYNAMICS
Voglibose -Voglibose, an alpha-glucosidase inhibitor, is a synthetic compound with potent and enduring therapeutic efficacies against disorders of sensory, motor and autonomic nerve systems due to diabetes mellitus. The drug was approved in Japan in 1994 for the treatment of diabetes, and it is under further investigation by Takeda for the treatment of impaired glucose tolerance. Alpha-glucosidase inhibitors are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of complex carbohydrates (such as starch). Complex carbohydrates are normally converted into simple sugars (monosaccharides) which can be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of complex carbohydrates on blood sugar.Metformin-Metformin is an oral antihyperglycemic agent that improves glucose tolerance in patients with NIDDM, lowering both basal and postprandial plasma glucose. Metformin is not chemically or pharmacologically related to any other class of oral antihyperglycemic agents. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with NIDDM or healthy subjects and does not cause hyperinsulinemia. Metformin does not affect insulin secretion.Glimpride -Glimepiride, like glyburide and glipizide, is a “second-generation” sulfonylurea agents. Glimepiride is used with diet to lower blood glucose by increasing the secretion of insulin from pancreas and increasing the sensitivity of peripheral tissues to insulin.
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ABSORPTION
Voglibose -Slowly and poorly absorbed.Metformin-Absorbed over 6 hours, bioavailability is 50 to 60% under fasting conditions. Administration with food decreases and delays absorption. Some evidence indicates that the level of absorption is not dose-related, suggesting that absorption occurs through a saturable process. Limited data from animal and human cell cultures indicate that absorption occurs through a passive, non-saturable process, possibly involving a paracellular route. Peak action occurs 3 hours after oral administration.Glimpride -Completely (100%) absorbed following oral administration.
VOLUME DISTRIBUTION
Metformin-654 L for metformin 850 mg administered as a single dose. The volume of distribution following IV administration is 63-276 L, likely due to less binding in the GI tract and/or different methods used to determine volume of distribution.Glimpride -21.8 ± 13.9 L [Volunteers], 19.8 ± 12.7 L [Patients with Type 2 diabetes, Single Dose], 37.1 ± 18.2 L [Patients with Type 2 diabetes, Multiple Dose].
METABOLISM
Voglibose -Little metabolism occurs and no metabolites have as yet been identified.Metformin-Metformin is not metabolized.Glimpride -Hepatic. Following either an intravenous or oral dose, glimepiride is completely metabolized by oxidative biotransformation to a major metabolite, cyclohexyl hydroxymethyl derivative (M1), via the hepatic cytochrome P450 II C9 subsystem. M1 is further metabolized to the carboxyl derivative (M2) by one or several cytosolic enzymes. M1, but not M2, possessed approximately one third of the pharmacologic activity of its parent in an animal model. However, whether the glucose-lowering effect of M1 is clinically significant is not clear.
ELIMINATION
Metformin-Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Approximately 90% of the drug is eliminated in 24 hours in those with healthy renal function. Renal clearance of metformin is approximately 3.5 times that of creatinine clearance, indicating the tubular secretion is the primary mode of metformin elimination. Glimpride –
HALF LIFE
Metformin-6.2 hours. Duration of action is 8-12 hours.Glimpride -Approximately 5 hours following single dose.
TOXICITY
Metformin-Acute oral toxicity (LD50): 350 mg/kg [Rabbit]. It would be expected that adverse reactions of a more intense character including epigastric discomfort, nausea, and vomiting followed by diarrhea, drowsiness, weakness, dizziness, malaise and headache might be seen.Glimpride -Severe hypoglycemic reactions with coma, seizure, or other neurological impairment.
FOOD INTERACTIONS
Metformin-Avoid alcohol. Take with food to reduce gastric irritation.Glimpride -Avoid alcohol. Even though food reduces product absorption, the manufacturer recommends taking the product with the first meal of the day.
SIDE EFFECTS
Voglibose -Hypoglycemia, flatulence, intestinal obstruction like symptoms, fulminant hepatitis, diarrhoea, loose stools, anorexia, nausea, vomiting, heartburn, anemia numbness, edema, blurred vision, hot flushes malaise, weakness, hyperkalemia, increased serum amylase. Hypoglycaemia.Metformin-Low blood sugar signs include, anger, shaking, a fast heartbeat, confusion, or sweating. Keep hard candies, glucose tablets, liquid glucose, or juice on hand for low blood sugar. – Belly pain. – Upset stomach or throwing up. Many small meals, good mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help. – Loose stools (diarrhea). – Not hungry. – Bad taste in your mouth. This most often goes back to normal. – Too much acid in the blood (lactic acidosis) may rarely happen.Glimpride -Low blood sugar. Signs include anger, shaking, a fast heartbeat, confusion, or sweating. Keep hard candies, glucose tablets, liquid glucose, or juice on hand for low blood sugar. Upset stomach or throwing up. Many small meals, good mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help. Weight gain.