Pregnancy Implications

Crosses the placenta. Hypoglycemia; ear defects reported; other malformations reported but may have been secondary to poor maternal glucose control/diabetes. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.

Canadian Brand Name

Albert® Glyburide; Apo-Glyburide®; Dia eta®; Euglucon®; Gen-Glybe; Novo-Glyburide; Nu-Glyburide; PMS-Glyburide; ratio-Glyburide

Glyburide Synonyms

Diabeta; Glibenclamide; Glybenclamide; Glybenzcyclamide

U.S Brand Name Glyburide

Dia eta®; Glynase® PresTab®; Micronase®

New Classification

The new classification system identifies four types of diabetes mellitus: type 1, type 2, "other specific types" and gestational diabetes. Arabic numerals are specifically used in the new system to minimize the occasional confusion of type "II" as the number "11." Each of the types of diabetes mellitus identified extends across a clinical continuum of hyperglycemia and insulin requirements.

Type 1 diabetes mellitus (formerly called type I, IDDM or juvenile diabetes) is characterized by beta cell destruction caused by an autoimmune process, usually leading to absolute insulin deficiency.^2,7 The onset is usually acute, developing over a period of a few days to weeks. Over 95 percent of persons with type 1 diabetes mellitus develop the disease before the age of 25, with an equal incidence in both sexes and an increased prevalence in the white population. A family history of type 1 diabetes mellitus, gluten enteropathy (celiac disease) or other endocrine disease is often found. Most of these patients have the "immune-mediated form" of type 1 diabetes mellitus with islet cell antibodies and often have other autoimmune disorders such as Hashimoto's thyroiditis, Addison's disease, vitiligo or pernicious anemia. A few patients, usually those of African or Asian origin, have no antibodies but have a similar clinical presentation; consequently, they are included in this classification and their disease is called the "idiopathic form" of type 1 diabetes mellitus.

Type 2 diabetes mellitus (formerly called NIDDM, type II or adult-onset) is characterized by insulin resistance in peripheral tissue and an insulin secretory defect of the beta cell.^2,7 This is the most common form of diabetes mellitus and is highly associated with a family history of diabetes, older age, obesity and lack of exercise. It is more common in women, especially women with a history of gestational diabetes, and in blacks, Hispanics and Native Americans. Insulin resistance and hyperinsulinemia eventually lead to impaired glucose tolerance. Defective beta cells become exhausted, further fueling the cycle of glucose intolerance and hyperglycemia. The etiology of type 2 diabetes mellitus is multifactorial and probably genetically based, but it also has strong behavioral components.

Types of diabetes mellitus of various known etiologies are grouped together to form the classification called "other specific types." This group includes persons with genetic defects of beta-cell function (this type of diabetes was formerly called MODY or maturity-onset diabetes in youth) or with defects of insulin action; persons with diseases of the exocrine pancreas, such as pancreatitis or cystic fibrosis; persons with dysfunction associated with other endocrinopathies (e.g., acromegaly); and persons with pancreatic dysfunction caused by drugs, chemicals or infections.

Epidemiology

About 90% of patients with diabetes mellitus have Type 2 diabetes. An estimated 150 million people worldwide have Type 2 diabetes, and this number is expected to double within the next 20 years. Most of the increase will stem from developing and threshold countries such as India and China. In the USA, where the prevalence of diabetes is high, it is estimated that one in three people will develop Type 2 diabetes.

Diabetes Types

Types:

There are three types of Diabetes:

• Type 1 Diabetes
• Type 2 Diabetes
• Gestational Diabetes

Type 1 diabetes

Type 1 diabetes is an autoimmune disease. In genetically susceptible individuals, an inflammation of pancreatic beta cells is triggered, most likely by a viral infection. Because beta cells are the only ones able to produce and secrete insulin, complete insulin deficiency ensues. As a result, all Type 1 diabetic patients require insulin replacement therapy. The only exception is during the 'honeymoon period' that some patients experience shortly after diagnosis and initial treatment, owing to some residual insulin secretion early in the progress of the disease.

Type 2 diabetes

Type 2 diabetes is a prime example of a disease caused by a combination of genetic and environmental factors. The genetic influence is greater than for Type 1 diabetes: the identical twin of a Type 2 diabetic patient is almost certain to develop the disease. On the other hand, lifestyle factors such as diet and exercise are also important determinants; in times of scarce food supply, for instance, the incidence of Type 2 diabetes is very low.

A good example of the interplay of genetics and lifestyle are the Pima Indians. Those living in Mexico have a diabetes prevalence of about 8%, whereas those who have emigrated to the USA, where the lifestyle is more sedentary and access to energy-dense (fatty) food is easier, have a diabetes prevalence of about 50%.

he most important risk factor for Type 2 diabetes is obesity. Epidemiological studies have shown that, compared to lean individuals, very obese men and women (body mass index >35) have a 60- and 90-fold increased probability of developing Type 2 diabetes, respectively (see figure). In terms of genetics, Type 2 diabetes is a multifactorial disease for which no single gene is responsible.

In contrast to patients with overt Type 2 diabetes, patients with pre-diabetes (characterised by insulin resistance) do not exhibit hyperglycaemia when fasting. However, after a challenge like an oral glucose tolerance test (oGTT), during which 75 grams of glucose are ingested, patients exhibit pathologically high glucose levels (see Table 1). These patients, therefore, are characterised as having impaired glucose tolerance.

For a limited period, pancreatic beta cells are able to produce enough insulin to overcome the insulin resistance, so many pre-diabetic patients actually have elevated plasma insulin levels. However, in most patients, the rate of beta-cell death exceeds that of beta-cell formation in the pancreas, resulting in fewer insulin-producing beta cells. When the insulin-producing capacity of the pancreas is overtaken by the increased demand caused by insulin resistance, the patient develops overt Type 2 diabetes.

Three main factors contribute to hyperglycaemia:

1. Insulin resistance in the muscle tissue, causing the muscles to take up less glucose from the blood.
2. Impaired insulin secretion by the pancreas.
3. Increased glucose production by the liver as a consequence of hepatic insulin resistance.

In the last few years, it has been demonstrated that adipose (fat) tissue and the central nervous system also play important roles in the pathogenesis of Type 2 diabetes.

Diabetics

Diabetes prevents your body from turning your food into energy. Instead glucose stays in your bloodstream, and left untreated can result in a range of complications.

If you have recently been diagnosed as diabetic, don't worry. With proper treatment and care, you will lead a normal and happy life. You may need to make a few changes in your lifestyle - but then, if you are like me, you probably had plans to do that anyway and just never got round to it.

Side Effects

Get emergency medical help if you have any of these symptoms of lactic acidosis: weakness, increasing sleepiness, slow heart rate, cold feeling, muscle pain, shortness of breath, stomach pain, feeling light-headed, and fainting. Stop using Glucovance and get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

• feeling short of breath, even with mild exertion; or

• swelling or rapid weight gain.

Other less serious side effects may be more likely to occur, such as:

• sneezing, runny nose, cough or other signs of a cold;

• headache;

• dizziness; or

• mild nausea, vomiting, diarrhea, stomach pain.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome.

How Should Take

Take this medication exactly as it was prescribed for you. Do not take the medication in larger or smaller amounts, or take it for longer than recommended by your doctor. Your doctor may occasionally change your dose to make sure you get the best results from this medication.

Take Glucovance with meals.

Glucovance is only part of a complete program of treatment that also includes diet, exercise, and weight control. It is important to use this medicine regularly to get the most benefit. Get your prescription refilled before you run out of medicine completely.

To be sure this medication is helping your condition, your blood will need to be tested on a regular basis. Your kidney function may also need to be tested. It is important that you not miss any scheduled visits to your doctor.

Your medication needs may change if you become sick or injured, if you have a serious infection, or if you have any type of surgery. Your doctor may want you to stop taking Glucovance for a short time if any of these situations affect you.

Take care not to let your blood sugar get too low, causing hypoglycemia. You may have hypoglycemia if you skip a meal, exercise too long, drink alcohol, or are under stress.

Know the signs of low blood sugar (hypoglycemia) and how to recognize them:

• hunger, headache, confusion, irritability;

• drowsiness, weakness, dizziness, tremors;

• sweating, fast heartbeat;

• seizure (convulsions); or

• fainting, coma (severe hypoglycemia can be fatal).

Always keep a source of sugar available in case you have symptoms of low blood sugar. Sugar sources include orange juice, glucose gel, candy, or milk. If you have severe hypoglycemia and cannot eat or drink, use an injection of glucagon. Your doctor can give you a prescription for a glucagon emergency injection kit and tell you how to give the injection.

Your doctor may have you take extra vitamin B12 while you are taking Glucovance. Take only the amount of vitamin B12 that your doctor has prescribed.

If you need to have any type of x-ray or CT scan using a dye that is injected into your veins, you may need to temporarily stop taking Glucovance. Be sure the surgeon knows ahead of time that you are using this medication.

Store Glucovance at room temperature away from moisture and heat.

What should I discuss with my healthcare provider before taking Glucovance

Some people have developed a life-threatening condition called lactic acidosis while taking Glucovance. Get emergency medical help if you have any of these symptoms of lactic acidosis: weakness, increasing sleepiness, slow heart rate, cold feeling, muscle pain, shortness of breath, stomach pain, feeling light-headed, and fainting.

You may be more likely to develop lactic acidosis if you have congestive heart failure.

Do not use Glucovance if you have congestive heart failure or kidney disease, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

Before taking this medication, tell your doctor if you have:

• heart disease;

• liver disease; or

• a history of heart attack or stroke.

If you have any of these conditions, you may not be able to use Glucovance, or you may need a dosage adjustment or special tests during treatment.

FDA pregnancy category B. This medication is not expected to be harmful to an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment. It is not known whether Glucovance passes into breast milk or if it could harm a nursing baby. Do not take Glucovance without first talking to your doctor if you are breast-feeding a baby. Older adults may have a higher risk of developing lactic acidosis. Talk with your doctor about your individual risk.

What is Glucovance

Glucovance is a combination of two oral diabetes medicines that help control blood sugar levels.

Glucovance is for people with type 2 diabetes who do not use daily insulin injections. This medication is not for treating type 1 diabetes.

Glucovance may also be used for purposes other than those listed in this medication guide.

Glucovance - Drug

GLUCOVANCE™ (Glyburide and Metformin HCl Tablets) contains two oral antihyperglycemic drugs used in the management of type 2 diabetes, glyburide and metformin hydrochloride.

Glyburide is an oral antihyperglycemic drug of the sulfonylurea class. The chemical name for glyburide is 1-[[ p -[2-(5-chloro- o -anisamido)ethyl]phenyl]sulfonyl]-3-cyclohexylurea. Glyburide is a white to off-white crystalline compound with a molecular formula of C 23 H 28 ClN 3 O 5 S and a molecular weight of 494.01. The glyburide used in GLUCOVANCE has a particle size distribution of 25% undersize value not more than 6 µm, 50% undersize value not more than 7-10 µm, and 75% undersize value not more than 21 µm.

Metformin hydrochloride is an oral antihyperglycemic drug used in the management of type 2 diabetes. Metformin hydrochloride ( N,N -dimethylimidodicarbonimidic diamide monohydrochloride) is not chemically or pharmacologically related to sulfonylureas, thiazolidinediones, or (alpha)-glucosidase inhibitors. It is a white to off-white crystalline compound with a molecular formula of C 4 H 12 ClN 5 (monohydrochloride) and a molecular weight of 165.63. Metformin hydrochloride is freely soluble in water and is practically insoluble in acetone, ether, and chloroform. The pKa of metformin is 12.4. The pH of a 1% aqueous solution of metformin hydrochloride is 6.68.

GLUCOVANCE is available for oral administration in tablets containing 1.25 mg glyburide with 250 mg metformin hydrochloride, 2.5 mg glyburide with 500 mg metformin hydrochloride, and 5 mg glyburide with 500 mg metformin hydrochloride. In addition, each tablet contains the following inactive ingredients: microcrystalline cellulose, povidone, croscarmellose sodium, and magnesium stearate. The tablets are film coated, which provides color differentiation.