GLUCOVANCE

Glucovansu

2009-11-05T10:49:00.001-08:00

Glucovance is cheap. If you do not have drug insurance, you can expect to pay about 50 cents per pill in the United States.

Many internet pharmacies sell Glucovance. This competition drives down the price of glucovance even lower. You can get a good price on glucovance if you comparison shop.

Pharmacies know that diabetics usually take many drugs. Sometimes they will give you a good price on glucovance, hoping to get the rest of your business.

Here are the top internet websites that sell gluconavce and other drugs. You can save money on gluconavce if you comparison shop.

Will glucovance get you high?

Q.-Do I need a prescription to order Glucovance?
A.-A prescription is NOT required to order Glucovance and other of our products.

Q.-What is the minimum and maximum amount I can order Glucovance at one time?
A.-We have no limits to how much you can order Glucovance.

Q.-How do I order Glucovance and can you explain your shopping cart process ?
A.-Ordering with Your-OnlinePharmacy.com is fast, easy and in real time. Simply press the BUY Glucovance button and order Glucovance online.

Strengths

2009-06-26T02:57:00.001-07:00

Glucovance tablets are available in three strengths:

Glucovance 1.25 mg/250 mg tablets -- containing 1.25 mg of glyburide and 250 mg of metformin
Glucovance 2.5 mg/500 mg tablets -- containing 2.5 mg of glyburide and 500 mg of metformin
Glucovance 5 mg/500 mg tablets -- containing 5 mg of glyburide and 500 mg of metformin.

Fact - Glucova

2009-06-26T02:52:00.001-07:00

Side-Effects

2009-04-09T09:27:00.000-07:00

Glucovance: Side Effects
Introduction to Glucovance

Licensed health care professionals may prescribe Glucovance for the treatment of type 2 diabetes. Glucovance is composed of two drugs known as glyburide and metformin. These drugs work together to attack high blood sugar levels.

Glyburide will stimulate insulin production in the pancreas. It will try to help the body use the insulin effectively. Metformin decreases sugar production and absorption. It also works to encourage the body’s effective use of insulin.
Diabetes

To understand Glucovance as a medical treatment, it is critical to understand that diabetes is an illness wherein the body is unable to control the level of sugar, (glucose) that is present in the body. Sugar is produced by the body, but may also be introduced to the human system through the consumption of starch based foods and foods that have been artificially sweetened.
Types of Diabetes

Diabetes will develop when a person’s body is unable to process sugar. This sugar will build up in the bloodstream. In most cases, patients will suffer from one of two major categories of diabetes. They are type 1 diabetes and type 2 diabetes.

Type 1 diabetes develops when the body is unable to produce insulin on its own. Patients may be treated with insulin injections, as well as modifications to diet and exercise regimes.

People who suffer from 2 diabetes usually develop the condition at 40 years of age or older. This type of diabetes occurs when the body is unable to create enough insulin to function, or is unable to process the insulin properly. This type of diabetes may also be treated with diet, exercise, and careful attention to maintenance of a healthy weight profile.
Complications of Diabetes

Medical professionals will attempt to reduce the likelihood of developing diabetes by encouraging their high risk patients to maintain a healthy weight, and adhere to diet and exercise routines. Doctors will advise patients that diabetes can negatively affect vision, and the functioning of major organs such as the heart and kidneys. Diabetic complications may also affect the feet, increase thirst, and create a feeling of extreme exhaustion.
Usage of Glucovance

Glucovance is an oral medication that may be taken up to twice per day with meals. Never take two doses at the same time, even if you have missed a dosage.
Side Effects of Glucovance

Glucovance is not a replacement for insulin treatment. This drug must be used in combination with regimes consisting of a healthy diet and adequate physical activity.

In general, usage of this drug may cause bouts of hunger, cold sweats, nausea, and dizziness. Others report generalized shakiness, development of anemia, stomach pain, vomiting, and upper respiratory infections.
Potential Complications of Glucovance

It is important to note that diabetic patients who utilize Glucovance must be aware that it can cause harmful reactions in the body. Some patients report episodes of hypoglycemia, or low blood sugar. Usage of this drug can also cause fatal complication in patients with kidney or liver deficiencies.

In some instances, Glucovance has induced lactic acidosis, which is a buildup of lactic acid in the blood. This medical emergency will require immediate professional care. Do seek attention from a physician if you notice stomach discomfort, unusual muscle pain or an irregular heartbeat.
Final Note

Glucovance may also negatively interact with medications that the patient already takes. For example, it may cause adverse reactions for patients who utilize birth control medications, cardiac prescriptions, thyroid medications, and antidepressants, among others. Given the high potential for health complications, patients must seek the advisement of a doctor prior to using, (or discontinuing the use of), Glucovance.

Metformin

2009-04-09T09:25:00.001-07:00

Metformin hydrochloride is an oral antihyperglycemic drug used in the management of type 2 dia-betes. Metformin hydrochloride (N, N-dimethylimidodicarbonimidic diamide monohydrochloride) is not chemically or pharmacologically related to sulfonylureas, thiazolidinediones, or -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 magne-sium stearate. The tablets are film coated, which provides color differentiation.

FDA Accept Glucovance

2009-04-09T09:24:00.000-07:00

Bristol-Myers Squibb Company announced that the U.S. Food and Drug Administration (FDA) has approved Glucovance™ (glyburide and metformin HCl tablets) for use, along with diet and exercise, as initial drug therapy for people with type 2 diabetes.

The drug was also approved as second-line therapy for patients with type 2 diabetes who are currently taking either or a sulfonylurea and a regimen of diet and exercise, but whose blood sugar levels are inadequately controlled.

Glucovance combines glyburide and glucophage -- the two most widely prescribed oral antidiabetic agents -- in a single pill. These agents work together to improve blood sugar in patients with type 2 diabetes.

"Glucovance represents a new approach to managing type 2 diabetes," said Richard J. Lane, president, Worldwide Medicines Group, Bristol-Myers Squibb. "It is our hope that the introduction of this novel agent could change the treatment paradigm for the more than 15 million patients in the U.S. with this condition."

Glucovance will be available in three dosing strengths, including 1.25 mg/250 mg (glyburide/metformin) tablets, 2.5 mg/500 mg tablets, and 5 mg/500 mg.

Glucovance has been proven safe and effective in clinical trials. In rare cases, Glucovance (or glucophage) may cause lactic acidosis, which can be fatal in up to half of the cases. Lactic acidosis occurs mainly in people whose kidneys are not functioning properly. Patients should not take these drugs if they have kidney problems, if they are 80 or older (unless they have their kidneys tested first), if they are taking medication for heart failure, if they have a history of liver disease or if they drink alcohol excessively. The most common side effects of Glucovance are normally minor ones such as diarrhea, nausea, and upset stomach. Less frequently, symptoms of hypoglycemia (low blood sugar) such as lightheadedness, dizziness, shakiness, or hunger may occur.

Uses

2009-04-09T09:23:00.000-07:00

Glucovance Uses : This anti-diabetic medication is a combination of two drugs (a sulfonylurea and a biguanide). It is used along with a diet and exercise program to control high blood sugar in patients with type 2 diabetes (non-insulin-dependent diabetes). Glucovance works by stimulating the release of your body s natural insulin and by restoring your body s proper response to insulin. Controlling high blood sugar helps prevent heart disease, strokes, kidney disease, blindness and circulation problems, as well as sexual function problems (impotence).

How to Use Glucovance : Take Glucovance by mouth, usually twice daily with meals; or as directed by your doctor. Drink plenty of fluids while taking Glucovance. Use Glucovance regularly in order to get the most benefit from it. To help you remember, use it at the same times each day. Your dosage is based on your medical condition and response to therapy. Glucovance may come with a Patient Information Leaflet. Read it carefully and ask your doctor or pharmacist any questions you may have about your medication.

Glucovance Side Effects : Also see Warning section. Nausea, stomach upset, diarrhea, or weight gain may occur initially as your body adjusts to the medication. If stomach symptoms recur later (after you are on the same dose for several days or weeks), tell your doctor immediately. A late recurrence of stomach symptoms may be due to lactic acidosis. Tell your doctor immediately if any of these highly unlikely but very serious side effects occur: persistent sore throat or fever, easy bleeding or bruising, severe stomach pain, yellowing eyes or skin, dark urine, unusual tiredness or weakness, unusual or sudden weight gain, mental/mood changes, swelling of the hands or feet, seizures. Glucovance can cause low blood sugar (hypoglycemia). This effect may occur if you do not consume enough calories (from food, juices, fruit, etc.). The symptoms include chills, cold sweat, blurred vision, dizziness, drowsiness, shaking, rapid heartbeat, weakness, headache, fainting, tingling of the hands or feet, or hunger. It is a good habit to carry glucose tablets or gel to treat low blood sugar. If you are in a situation where you don t have these reliable forms of glucose, eat a quick source of sugar such as table sugar, honey, or candy, or drink a glass of orange juice or non-diet soda to quickly raise your blood sugar level. Tell your doctor immediately about the reaction. To help prevent hypoglycemia, eat meals on a regular schedule and do not skip meals. Symptoms of high blood sugar (hyperglycemia) include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, or fruity breath odor. If these symptoms occur, tell your doctor immediately. Your medication dosage may need to be increased. An allergic reaction to Glucovance is unlikely, but seek immediate medical attention if it occurs. Symptoms of an allergic reaction include: rash, itching, swelling, dizziness, trouble breathing. If you notice other effects not listed above, contact your doctor or pharmacist.

Glucovance Precautions : Glucovance should not be used if you have certain medical conditions. Before using Glucovance, consult your doctor or pharmacist if you have: kidney disease, liver disease, conditions that may cause a low oxygen blood level or poor circulation (e.g., severe congestive heart failure, recent heart attack, recent stroke), metabolic conditions (e.g., diabetic ketoacidosis), serious infection, lack of body fluids (dehydration). Before using Glucovance, tell your doctor or pharmacist your medical history, especially of: severe breathing problems (e.g., obstructive lung disease, severe asthma), thyroid disease, blood problems (e.g., anemia, vitamin B-12 deficiency), scheduled upcoming surgery, scheduled upcoming x-ray or scanning procedures, alcohol use, certain hormonal conditions (adrenal/pituitary insufficiency, SIADH-syndrome of inappropriate secretion of antidiuretic hormone), electrolyte imbalance (hyponatremia), high blood pressure, fertility problems (e.g., ovulation problems), any allergies. You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcohol while taking Glucovance because it can increase the risk of developing hypoglycemia. Rarely, alcohol can interact with glyburide and cause a serious reaction (disulfiram-like reaction) with symptoms such as facial flushing, nausea, vomiting, dizziness, or stomach pain. Consult your doctor or pharmacist about the safe use of alcohol. During times of stress, such as fever, infection, injury or surgery, it may be more difficult to control your blood sugar. Consult your doctor, as a change in your medication may be required. Glucovance may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths or sunlamps. Use a sunscreen and wear protective clothing when outdoors. Caution is advised when using Glucovance in the elderly because they may be more sensitive to the effects of Glucovance. Glucovance can cause changes in the menstrual cycle (promote ovulation) in women with certain fertility problems, increasing the risk of becoming pregnant. Consult your doctor or pharmacist about the use of reliable birth control while using Glucovance. Glucovance should be used only when clearly needed during pregnancy. It is not recommended for use for at least 2 weeks before delivery due to the potential for fetal harm. Insulin may be preferred during pregnancy. Discuss the risks and benefits with your doctor. Based on information from related drugs, Glucovance may pass into breast milk. Breast-feeding is not recommended while using Glucovance.

Glucovance Interactions : Glucovance should not be used with the following medications because very serious interactions may occur: bosentan. If you are currently using any of these medications, tell your doctor or pharmacist before starting glyburide/metformin. Before using Glucovance, tell your doctor or pharmacist of all prescription and nonprescription products you may use, especially of: other diabetes drugs (e.g., insulin, rosiglitazone), aspirin or aspirin-like drugs (e.g., salicylates, NSAIDs such as ibuprofen, phenylbutazone), azole antifungals (e.g., fluconazole), cimetidine, birth control pills, blood thinners (e.g., warfarin), chloramphenicol, clofibrate, clomiphene, corticosteroids (e.g., prednisone), decongestants (e.g., pseudoephedrine), diazoxide, diet pills, epinephrine, estrogens, high blood pressure drugs (beta-blockers -- including glaucoma eye drops such as propranolol, timolol, metoprolol; calcium channel blockers such as nifedipine; ACE inhibitors such as captopril), isoniazid, MAO inhibitors (e.g., furazolidone, linezolid, moclobemide, phenelzine procarbazine, selegiline, isocarboxazid, tranylcypromine), niacin, phenothiazines (e.g., chlorpromazine), phenytoin, probenecid, quinolone antibiotics (e.g., ciprofloxacin), rifampin, sulfonamides (e.g., sulfa antibiotics), thyroid drugs, water pills (diuretics such as hydrochlorothiazide, furosemide), fenugreek, ginseng. If you are scheduled to undergo any x-ray or scanning procedure using injectable iodinated contrast material, be sure to inform your doctor that you are taking Glucovance. You will need to temporarily stop Glucovance around the time of your procedure. Consult your doctor for further instructions. Do not start or stop any medicine without doctor or pharmacist approval.

Overdose of Glucovance : If overdose is suspected, contact your local poison control center or emergency room immediately. Symptoms of overdose may include: rapid or trouble breathing, severe drowsiness, fast/slow/irregular heartbeat, shakiness, sweating, loss of consciousness.

Glucovance : If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Storing Glucovance : Store at room temperature (77 degrees F or 25 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Glucovance

2009-04-09T09:18:00.000-07:00

Glucovance Side Effects
Also see Warning section. Nausea, stomach upset, diarrhea, or weight gain may occur initially as your body adjusts to the medication. If stomach symptoms recur later (after you are on the same dose for several days or weeks), tell your doctor immediately. A late recurrence of stomach symptoms may be due to lactic acidosis. Tell your doctor immediately if any of these highly unlikely but very serious side effects occur: persistent sore throat or fever, easy bleeding or bruising, severe stomach pain, yellowing eyes or skin, dark urine, unusual tiredness or weakness, unusual or sudden weight gain, mental/mood changes, swelling of the hands or feet, seizures. Glucovance can cause low blood sugar (hypoglycemia). This effect may occur if you do not consume enough calories (from food, juices, fruit, etc.). The symptoms include chills, cold sweat, blurred vision, dizziness, drowsiness, shaking, rapid heartbeat, weakness, headache, fainting, tingling of the hands or feet, or hunger. It is a good habit to carry glucose tablets or gel to treat low blood sugar. If you are in a situation where you don t have these reliable forms of glucose, eat a quick source of sugar such as table sugar, honey, or candy, or drink a glass of orange juice or non-diet soda to quickly raise your blood sugar level. Tell your doctor immediately about the reaction. To help prevent hypoglycemia, eat meals on a regular schedule and do not skip meals. Symptoms of high blood sugar (hyperglycemia) include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, or fruity breath odor. If these symptoms occur, tell your doctor immediately. Your medication dosage may need to be increased. An allergic reaction to Glucovance is unlikely, but seek immediate medical attention if it occurs. Symptoms of an allergic reaction include: rash, itching, swelling, dizziness, trouble breathing. If you notice other effects not listed above, contact your doctor or pharmacist.

Glucovance Precautions
Glucovance should not be used if you have certain medical conditions. Before using Glucovance, consult your doctor or pharmacist if you have: kidney disease, liver disease, conditions that may cause a low oxygen blood level or poor circulation (e.g., severe congestive heart failure, recent heart attack, recent stroke), metabolic conditions (e.g., diabetic ketoacidosis), serious infection, lack of body fluids (dehydration). Before using Glucovance, tell your doctor or pharmacist your medical history, especially of: severe breathing problems (e.g., obstructive lung disease, severe asthma), thyroid disease, blood problems (e.g., anemia, vitamin B-12 deficiency), scheduled upcoming surgery, scheduled upcoming x-ray or scanning procedures, alcohol use, certain hormonal conditions (adrenal/pituitary insufficiency, SIADH-syndrome of inappropriate secretion of antidiuretic hormone), electrolyte imbalance (hyponatremia), high blood pressure, fertility problems (e.g., ovulation problems), any allergies. You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcohol while taking Glucovance because it can increase the risk of developing hypoglycemia. Rarely, alcohol can interact with glyburide and cause a serious reaction (disulfiram-like reaction) with symptoms such as facial flushing, nausea, vomiting, dizziness, or stomach pain. Consult your doctor or pharmacist about the safe use of alcohol. During times of stress, such as fever, infection, injury or surgery, it may be more difficult to control your blood sugar. Consult your doctor, as a change in your medication may be required. Glucovance may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths or sunlamps. Use a sunscreen and wear protective clothing when outdoors. Caution is advised when using Glucovance in the elderly because they may be more sensitive to the effects of Glucovance. Glucovance can cause changes in the menstrual cycle (promote ovulation) in women with certain fertility problems, increasing the risk of becoming pregnant. Consult your doctor or pharmacist about the use of reliable birth control while using Glucovance. Glucovance should be used only when clearly needed during pregnancy. It is not recommended for use for at least 2 weeks before delivery due to the potential for fetal harm. Insulin may be preferred during pregnancy. Discuss the risks and benefits with your doctor. Based on information from related drugs, Glucovance may pass into breast milk. Breast-feeding is not recommended while using Glucovance.

The Symlin Pen

2009-02-19T06:15:00.000-08:00

The FDA approved pre-filled Symlin pens in November of 2007 and Amylin made them available in January of 2008. Previously, it was only available in vials. There are currently two pens available: the SymlinPen 60 and 120. The SymlinPen 60 delivers 15, 30, 45, or 60 micrograms per dose. The SymlinPen 120 delivers 60 or 120 micrograms per dose. Both may be stored at room temperature, up to 86 degrees, after first use.

Symlin, An Injectable Form of Amylin

2009-02-19T06:14:00.000-08:00

During the destruction of beta cells in Type 1 or Type 1.5 diabetes by friendly fire from antibodies, the body actually loses two hormones. And similar to insulin, Amylin production may fall in Type 2 diabetes over time. Amylin is normally co-secreted alongside insulin and, like insulin, is released by the beta cells around the clock with larger amounts released at mealtimes.

Insulin was the first of the two hormones to be discovered because it was so critical to survival. It was not until 1970 that amylin was discovered, and not until the early 1990s is that its role began to be understood. Not essential for life, amylin plays an important role in glucose regulation by slowing digestion and suppressing an excessive release of glucagon that is seen after meals in Type 1 diabetes. The excess glucagon rise seen in Type 1 diabetes causes additional glucose release by the liver at mealtimes. The release of amylin at mealtimes minimizes the glucose spikes that are often seen in Type 1 diabetes after meals.

Symlin is a modified longer-acting form of amylin that was released by the FDA in 2005. This prescription medication dramatically improves post meal glucose control and reduces glucose variability and glucose exposure in anyone whose insulin production is limited. Symlin decreases glucagon secretion, decreases appetite, and delays gastric emptying. When injected before meals, post meal blood sugars become easier to control. Users often comment that they feel better with more stable glucose readings.

One caution when starting on Symlin is that it can cause severe low blood sugars if meal insulin doses are not lowered on the day it is started and for at least the first few days of use. If meal insulin doses are not reduced, up to 30% of users experience severe hypoglycemia within about 3 hours of eating. To reduce the risk of hypoglycemia, Symlin is started at very small doses and then gradually increased every few days until the desired effect is seen. Meal insulin doses are typically reduced by 30% to 50% when starting and later adjusted based on pre and post meal glucose results once a final Symlin dose is reached. Long-acting insulin doses or basal rates may also need to be lowered, especially if these make up more then 50% of the starting TDD (total daily dose of insulin). As weight loss occurs in someone who is overweight, additional insulin reductions will be needed over time.

Dosing
Symlin is injected with a standard insulin syringe, so dosing is flexible. How much to use depends on what it is used for. For weight loss, maximum doses are usually best, while lower doses often work when the goal is to normalize post-meal glucose levels. The manufacturer recommends starting with 2.5 units and increasing to 5 units, then 7.5 units, and 10 units before each meal if no nausea is encountered for three days.

However, different people will require very different doses and we recommend that Symlin doses be individualized in the same way as insulin doses. If your goal is to reduce post meal spiking and glucose variability, raise the Symlin dose by one unit every three days until you reach a dose where most of your post meal blood sugar readings rise no more than 40 to 60 mg/dl (2.2 to 3.3 mmol) above where they started. The idea is to take enough to have good post meal control (less variability) without overly delaying the normal rise in glucose after a meal (less problem correcting a low reading). Keep raising the Symlin or increasing meal boluses until post meal readings are consistently less than 60 mg/dl (3.3 mmol) higher than the premeal readings. The correct doses of Symlin and insulin allow you to keep most post meal readings from rising much while causing few lows. In many Type 1s, only 2 to 6 units taken two or three times a day before meals are required to do this. Symlin is usually taken just before meals that contain at least 250 calories or 30 grams of carbohydrate. If a dose is missed, wait until the next meal to take the regular scheduled dose.

Your current TDD for insulin can guide your premeal Symlin dose. Approximately 10% of your insulin TDD is needed as Symlin before each meal. For instance, if you use 40 units of insulin a day you will need approximately 4 units of Symlin before each meal to control your post meal readings. For weight loss, of course, larger amounts will be needed. A safer way to increase Symlin is to start with 2 units before two or three meals a day, or 1 unit if your TDD is less than 30 units of insulin a day. Increase by 1 unit per meal every three days as long as nausea is not present.

Post meal Control
Glucose spiking after meals can be totally eliminated at higher doses, with flat glucose trend lines often seen on a continuous monitor. At higher Symlin doses, however, if a large carb meal is consumed, the rise in the blood sugar may not be seen until several hours later, such as a high reading at breakfast the next morning after a large carb intake at dinner. Matching injected insulin doses to Symlin can be difficult. Today's rapid insulins become too fast when larger doses of Symlin are used. If you inject your insulin, the use of a slower insulin like Regular may be preferred.

On a pump, a combo bolus (some now, the rest over time) or an extended bolus can be used to match the slower rise in glucose after meals. If a blood sugar is low before a meal, raise it before taking Symlin. Reduce the meal bolus and give it as an extended bolus. If Symlin doses are missed for more than two or three days, do not restart with full doses. Instead, restart at a lower dose and build up to lessen the risk of hypoglycemia.

Weight Loss
Less hunger allows some people who are overweight to lose significant amounts of weight, while normal weight individuals lose none. Symlin is currently undergoing studies for approval by the FDA as a weight loss drug.

For weight loss, the dose may occasionally need to go higher.

Stability
Symlin is less stable than insulin. If one bottle of Symlin appears to have no effect on your blood sugar try another bottle. Symlin activity is more vulnerable to time and temperature than insulin and can lose significant activity, especially if a sample bottle was handed out from a physician's office. If you seem to get little effect from a bottle, start a fresh bottle at a lower dose. Excess doses are easy to spot by a feeling of fullness or nausea after the dose is given. Vomiting and diarrhea may occur on an excessive dose. If side effects occur, simply lower the dose by one or 2 units. Increase the dose again after there is no fullness or nausea for at least three days.

Tips On Handling Lows
Symlin delays the digestion of all food, including the carbs you use to raise a low blood sugar. If a low occurs, use glucose tablets if available and chew them as long as possible to allow more glucose to be absorbed directly into the bloodstream. Be patient, as the rise in your glucose will be slowed because of Symlin. Likewise when lowering a high reading with insulin, it will take longer and may require larger than normal insulin doses because food is still being absorbed.

Lantus

2009-02-19T06:07:00.000-08:00

Lantus® (insulin glargine [rDNA origin] injection) is a new true once a day background insulin from Aventis Pharmaceuticals. It represents a remarkable breakthrough in that it is the first insulin to offer truly flat insulin levels through the entire day for most users. It can be used by people with Type 1 or Type 2 diabetes who are six years old or older. Considered an alternative to an insulin pump, it is the first long-term insulin that has a predictable and consistent insulin activity.

Tips For Starting
Morning or night? Aventis recommends taking Lantus at bedtime. Lantus' actual duration of action is 18 to 26 hours. Although the timing varies from indiviual to individual, it appears to be consistent in the same indiviual. The advantage to bedtime dosing is that for most people any gap in Lantus' activity would happen after dinner and this gap could be covered with a little extra Humalog or Novolog in the dinner injection.

Whether you take it at bedtime or breakfast, it helps to be consistent about timing, so pick a time when you will remember to take the injection at the same time each day.

A good way to eliminate any gaps in insulin delivery, whether caused by a duration of action less than 24 hours or by erratic timing of injections is to split the Lantus dose equally into 2 injections a day given at breakfast and at dinner or bedtime. This smoothes out the sometimes erratic insulin levels that may occur with once a day dosing.

Lantus is a clear insulin which is unlike other long-acting insulins (Lente, NPH, Ultralente) that are all cloudy. Although the bottles have a different shape, some users have already injected a bedtime dose of Humalog rather than Lantus! Be very careful not to confuse Lantus with Humalog and other clear insulins.

DO NOT MIX Lantus with any other insulin. Do not even reuse a syringe in Lantus that has come in contact with another insulin.

Lantus becomes inactivated if it comes in contact with even small amounts of other insulins. This makes it appear hazy. Never use any Lantus that is not crystal clear.

Lantus cannot replace the need for Humalog or another fast insulin to cover carbs in meals. However, occasionally in people with Type 2 diabetes, when the before breakfast blood sugar is normalized with Lantus, a premeal medication like Starlix, Prandin, or even Precose may be able to control the post meal blood sugars.

How Do I Know When I'm On The Right Dose?
One really nice feature of Lantus is that it makes finding the correct dose easy. Because of its very stable 24 hour action, the dose is gradually increased until the fasting or before breakfast blood sugar has been normalized. If low blood sugars occur during the night and they are not being caused by a dose of fast acting insulin taken during the evening hours, the dose of Lantus would be gradually reduced until the lows stop.

Similar to the basal rate of an insulin pump, the Lantus dose can be checked by skipping a meal during the day, but the real test for whether the dose is accurate comes from stable, flat overnight blood sugars.

Once the Lantus dose has been determined, the doses of premeal Humalog, Novalog, Starlix, etc. would then be adjusted to keep postmeal blood sugars normal. With a stable background insulin, carb counting becomes especially helpful as a way to decide on the insulin dose before each meal.

How Lantus Works
This insulin analog was designed to have low solubility in water at a neutral pH, such as that found in body fluids and other insulins. Lantus becomes completely soluble only at an acid pH of 4. Once this is injected under the skin, the acidic solution is neutralized leading to the formation of microprecipitates. The microprecipitates allow small amounts of insulin to be released slowly, resulting in a relatively constant concentration/time profile over 22 hours +/- 4 hours with no pronounced peak in activity.

Lantus was modified to allow this precise action. Normal insulin has two protein chains called A and B that have two zinc crosslinks between them. Lantus differs from other insulins in that one asparagine at position A21 of the A chain is replaced by glycine, and two arginines have been added added to one end of the B-chain.

Cautions
Occasionally, the acidic nature of this insulin may cause mild discomfort at the injection site in some individuals. This does not appear serious enough to cause users to discontinue the insulin.

Like Humalog, Lantus is structurally different from human insulin, but it appears to rarely cause an immune or allergic response. Like any insulin allergy, the response can range from a mild local itching to a severe allergic reaction with swelling of the tongue, inability to breath and shock or death if rapid treatment is not found.

Lantus should be used with great caution and only under the supervision of a physician during pregnancy or prior to pregnancy.

How Often Does Lantus Fail To Work?
How many people fail to respond to Lantus is unknown. The vast majority of users get a consistent action from this insulin every day. However, Aventis' clinical studies did pick up some individuals who had marked differences in the action time for Lantus from one day to the next. In rare individuals, it's action time was as short as 11 hours, but it is unknown why this difference occurs.

Lantus may not work for everyone, but for the vast majority who are willing to take an extra injection or two a day in order to get terrific control, this insulin is definitely worth a try.

Lilac plant

2009-02-19T05:50:00.000-08:00

Metformin is a chemical kin to the French lilac plant, which was noted in the early 1900’s to lower the blood sugar. However, French lilac, like phenformin, turned out to be too toxic for use in humans. Metformin, with a much shorter action time than phenformin, has a much lower risk for severe side effects and is quite safe for use by anyone who is otherwise healthy. In fact, in the major UKPDS study, it was the only drug that reduced diabetes-related death rates, heart attacks, and strokes. It should not be used by those who use more than two ounces or two drinks of alcohol a day, who have congestive heart failure, or who have significant kidney, liver, or lung disease.

Metformin lowers fasting blood glucose levels by an average of 25% (17 to 37%), postprandial blood glucose up to 44.5%, and the A1c by an average of 1.5% (0.8 to 3.1%). Metformin reduces raised plasma insulin levels in cases of metabolic syndrome by as much as 30% and reduces the need for injected insulin in Type 2s by 15 to 32%.

Metformin is available under the trade name Glucophage, or as an extended-release tablet called Glucophage XR. It works well when combined with sulfonylureas. A combination of glyburide and metformin is available as Glucovance. Combined therapy leads to a greater reduction in blood sugar than can be attained by either class alone. Generic metformin is available at a reduced cost.

Metformin possesses some distinct advantages in treating diabetes. Excess glucose produced by the liver is the major source of high blood sugars in Type 2 diabetes and is typically the reason for high blood sugars on waking in the morning. Metformin reduces this overproduction of glucose. It helps in lowering the blood sugar, especially after eating, with no risk of hypoglycemia when used alone. Modest improvement in cholesterol levels are also seen. The 10 year UKPDS Study of over 3,000 people with Type 2 diabetes found that those who were placed on metformin had a 36% decrease in overall mortality and a 39% decrease in heart attacks.

Because metformin shuts off the liver’s excess production of glucose, it reduces the amount of injected insulin needed to control the blood sugar in both Type 1 and Type 2 diabetes. People with Type 2 diabetes who are on insulin usually are advised to lower their insulin doses prior to starting metformin. The full improvement in glycemic control and cholesterol levels may not be seen until 4 to 6 weeks of use have passed.

Side effects from metformin include a change in taste, loss of appetite, nausea or vomiting, abdominal bloating or gas, diarrhea, or skin rash. These may occur during the first few weeks of taking the medication but are seldom long-lasting. Taking the medication with food and starting out with a low dose help reduce side effects. The dosage can be gradually increased as side effects diminish.

Lactic acidosis, the serious but rare side effect originally seen with phenformin, results when a buildup of lactic acid occurs due to an inability to clear metformin from the system. Lactic acidosis occurs very rarely, only once in every 30,000 person-years of use. It almost always occurs in older people who have another major health problem, especially one that may impair breathing or circulation. Warning signs of lactic acidosis include fast and shallow breathing, diarrhea, severe muscle aches, cramping, unusual weakness or tiredness, or feeling cold. Because lactic acidosis has a mortality rate of about 40%, anyone who has significant lung disease, congestive heart failure, or kidney disease should never take this drug.

Because drinking alcohol while taking metformin may also trigger lactic acidosis when other health risks are present, be sure to ask your doctor about alcohol consumption if you are taking this drug. Be aware that Tagamet, a gastrointestinal medication, may enhance the effects of metformin. Therefore, the dose of metformin may need to be lower if you already take Tagamet.

Although not yet FDA approved, metformin is now in clinical trials for treatment of teens who have developed Type 2 diabetes. Some pediatricians also prescribe it, on occasion, to help control a strong Dawn Phenomenon seen in a growing teen with Type 1 diabetes. This use is also not approved. It also helps lower insulin resistance in women with polycystic ovary disease. One side-effect for these women, sometimes a desired outcome, is a greater likelihood of pregnancy.

Nutrition Plan

2009-01-22T07:02:00.001-08:00

Nutrition Plan does not count calories. Instead, it gradually directs your body to a healthy diet. In essence, it provides the solution to one of the primary causes of Insulin Resistance and excess weight and obesity - too many carbohydrates. The Nutrition Plan also addresses the addictive quality of certain foods and advocates a high-protein, low-carbohydrate diet, with lots of green vegetables and fruits. We don't have an "induction phase" where you're deprived of all carbs and are just eating protein and fat. We ask that you lower your carbohydrate intake from where you are now and slowly persevere in reducing it each week, so it doesn't feel like such a shock to your system.

Glucovance

2009-01-12T07:16:00.000-08:00

In August, Bristol-Myers Squibb released an improved version of their popular diabetes pill, Glucophage. The new medication called Glucovance combines Glucophage with another well known glucose lowering medication, glyburide. Glyburide is also marketed under the brand name Micronase. Glyburide is a member of the class of drugs known as sulfonylureas which also includes, Glucotrol (glipizide), and Amaryl (glimepiride) while Glucophage is the only available drug in the class of biguinides. Glucovance offers a one-two punch on high blood sugar by joining the unique effects of its two components drugs into a single, even more powerful combination. Studies show that two thirds (66%) of diabetics will achieve excellent control of their blood sugars as defined by the American Diabetes Association (a glycohemoglobin A1c level of 7% or less), when using Glucovance. Since lower doses of Glucophage and glyburide are used in the combination pill then when used individually, there have been less side-effects, as well. It should be noted that although hypoglycemia (low blood sugar) is generally not seen when taking Glucophage alone, due to the additive effect of glyburide, hypoglycemia is possible when using Glucovance.

How does this new drug achieve such impressive results? Type 2 diabetes, which comprises about 90% of all diabetes in the U.S., is caused by a lack of the glucose regulating hormone, insulin, as well as a resistance by the body to the effects of whatever insulin is in the blood. Glyburide increases the production of insulin by the pancreas and Glucophage restores the body’s normal sensitivity to the insulin, thereby simultaneously reversing both of the major metabolic abnormalities that cause diabetes.

Cynical health care consumers will snicker, “Sure it’s a great drug. If you can afford it!!” Believe it or not, Glucovance is actually cheaper than purchasing the two component drugs separately, and is about the same price as Glucophage alone. You therefore get the second medication, glyburide, for free. For that reason cost conscious managed care organizations and HMO’s are lining up to put Glucovance on their formularies.

Glucovance is now approved to be used by itself as “first line” diabetes treatment, for those not controlled with either Glucophage or sulfonylurea alone, or can replace both medications if the patient is already using them in combination.

Only you and your doctor can decide which of the available diabetes drugs will be best for you. Be sure to visit your health care provider to learn more about this exciting new addition to diabetes treatment.

Glucovance Overdose

2008-11-24T07:52:00.002-08:00

If overdose is suspected, contact your local poison control center or emergency room immediately. Symptoms of overdose may include: rapid or trouble breathing, severe drowsiness, fast/slow/irregular heartbeat, shakiness, sweating, loss of consciousness. If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

Glucovance Side effects

2008-11-24T07:52:00.001-08:00

Nausea, stomach upset, diarrhea, or weight gain may occur initially as your body adjusts to the medication. A late recurrence of stomach symptoms may be due to lactic acidosis. Tell your doctor immediately if any of these highly unlikely but very serious side effects occur: persistent sore throat or fever, easy bleeding or bruising, severe stomach pain, yellowing eyes or skin, dark urine, unusual tiredness or weakness, unusual or sudden weight gain, mental/mood changes, swelling of the hands or feet, seizures. Glucovance can cause low blood sugar (hypoglycemia). This effect may occur if you do not consume enough calories (from food, juices, fruit, etc.). The symptoms include chills, cold sweat, blurred vision, dizziness, drowsiness, shaking, rapid heartbeat, weakness, headache, fainting, tingling of the hands or feet, or hunger. It is a good habit to carry glucose tablets or gel to treat low blood sugar. If you are in a situation where you don't have these reliable forms of glucose, eat a quick source of sugar such as table sugar, honey, or candy, or drink a glass of orange juice or non-diet soda to quickly raise your blood sugar level. Tell your doctor immediately about the reaction. To help prevent hypoglycemia, eat meals on a regular schedule and do not skip meals. Symptoms of high blood sugar (hyperglycemia) include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, or fruity breath odor. If these symptoms occur, tell your doctor immediately. Your medication dosage may need to be increased. A serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction include: rash, itching, swelling, dizziness, trouble breathing.

Glucovance Warnings

2008-11-24T07:51:00.002-08:00

The metformin in this combination medication can rarely cause a condition called lactic acidosis, which can be fatal. Seek immediate medical attention if you develop any of the following symptoms of lactic acidosis: unusual tiredness (fatigue) or severe drowsiness, cold skin, muscle pain, breathing trouble or rapid breathing, unusually slow or irregular heartbeat. Lactic acidosis is more likely to occur in patients who have: kidney or liver disease, conditions that may cause a low oxygen blood level or poor circulation (e.g., severe congestive heart failure, recent heart attack, recent stroke), excessive alcohol use, a lack of body fluids (dehydration), X-ray or scanning procedures that require an injectable iodinated contrast drug, surgery, or a serious infection. The elderly are also at higher risk, and have not had kidney and liver tests. Before taking glyburide and metformin, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: kidney disease, liver disease, conditions that may cause a low oxygen blood level or poor circulation (e.g., severe congestive heart failure, recent heart attack, recent stroke), metabolic conditions (e.g., diabetic ketoacidosis), serious infection, lack of body fluids (dehydration). Before using this medication, tell your doctor or pharmacist your medical history, especially of: severe breathing problems (e.g., obstructive lung disease, severe asthma), thyroid disease, blood problems (e.g., anemia, vitamin B-12 deficiency), scheduled upcoming surgery, scheduled upcoming X-ray or scanning procedures, alcohol use, certain hormonal conditions (adrenal/pituitary insufficiency, SIADH-syndrome of inappropriate secretion of antidiuretic hormone), electrolyte imbalance (Hyponatremia), fertility problems (e.g., ovulation problems).

You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels; use caution engaging in activities requiring alertness such as driving or using machinery. Limit alcohol while taking this medication because it can increase the risk of developing hypoglycemia. Rarely, alcohol can interact with glyburide and cause a serious reaction (disulfiram-like reaction) with symptoms such as facial flushing, nausea, vomiting, dizziness, or stomach pain. Consult your doctor or pharmacist about the safe use of alcohol. During times of stress, such as fever, infection, injury or surgery, it may be more difficult to control your blood sugar. Consult your doctor, as a change in your medication may be required. This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths or sunlamps. Use a sunscreen and wear protective clothing when outdoors. Caution is advised when using this drug in the elderly because they may be more sensitive to its effects. This medication can cause changes in the menstrual cycle (promote ovulation) in women with certain fertility problems, increasing the risk of becoming pregnant. Consult your doctor or pharmacist about the use of reliable birth control while using this medication. This medication should be used only when clearly needed during pregnancy. It is not recommended for use for at least 2 weeks before delivery due to the potential for fetal harm. Insulin may be preferred during pregnancy. Discuss the risks and benefits with your doctor. Based on information from related drugs, this medication may pass into breast milk. Breast-feeding is not recommended while using this drug Glucovance should not be used with bosentan .

Before using Glucovance , tell your doctor or pharmacist of all prescription and nonprescription products you may use, especially of: other diabetes drugs (e.g., insulin, rosiglitazone), aspirin or aspirin-like drugs (e.g., salicylates, NSAIDs such as ibuprofen, phenylbutazone), azole antifungals (e.g., fluconazole), cimetidine, birth control pills, "blood thinners" (e.g., warfarin), chloramphenicol, clofibrate, clomiphene, corticosteroids (e.g., prednisone), decongestants (e.g., pseudoephedrine), diazoxide, diet pills, epinephrine, estrogens, high blood pressure drugs (beta-blockers -- including glaucoma eye drops such as propranolol, timolol, metoprolol; calcium channel blockers such as nifedipine; ACE inhibitors such as captopril), isoniazid, MAO inhibitors (e.g., furazolidone, linezolid, moclobemide, phenelzine procarbazine, selegiline, isocarboxazid, tranylcypromine), niacin, phenothiazines (e.g., chlorpromazine), phenytoin, Probenecid, quinolone antibiotics (e.g., ciprofloxacin), rifampin, sulfonamides (e.g., sulfa antibiotics), thyroid drugs, "water pills" (diuretics such as hydrochlorothiazide, furosemide), fenugreek, ginseng. If you are scheduled to undergo any X-ray or scanning procedure using injectable iodinated contrast material, be sure to inform your doctor that you are taking this medication. You will need to temporarily stop this medication around the time of your procedure.

Information

2008-11-24T07:51:00.001-08:00

Glucovance is an anti-diabetic medication which is a combination of two drugs (sulfonylurea and biguanide). It is used along with a diet and exercise program to control high blood sugar in patients with type 2 diabetes (non-insulin-dependent diabetes). This medication works by stimulating the release of your body's natural insulin and by restoring your body's proper response to insulin. Controlling high blood sugar helps prevent heart disease, strokes, kidney disease, blindness and circulation problems, as well as sexual function problems (impotence).

Diabetes is hereditary, lifestyle triggers it

2008-11-24T07:50:00.001-08:00

A person may be genetically predisposed to diabetes, but lifestyle is what actually makes the individual become diabetic.
Speaking at the launch of Glucovance, a drug for the management of diabetes, Mr Femi Soremekun, Managing Director, Biofem Pharmaceuticals Limited, explained that the genes which we get from our parents "loads the gun" of type 2 diabetes, but the environment "pulls the trigger."

He also disclosed that there is no rigid prescribed diet plan for those with diabetes. Rather, eating plans are tailored to fit an individual’s needs, schedules, and eating habits.
Soremekun said a diabetes diet plan must also be combined with the intake of appropriate diabetes medications, pointing out that calucovance promises to introduce a new dimension in diabetes medication.

According to him, "diabetes remains a leading cause of blindness, amputation, renal failure and heart attack. Type I diabetes continuously occurs in early childhood, while type 2 diabetes generally occur in the middle age and the elderly. There have, however, been recent reports of type 2 diabetes occurring in children and adolescents. People, who only have diabetes only when they are pregnant are said to have gestational diabetes.

"The rate of death arising from diabetes mellitus in developing countries is becoming worrisome. Diabetes, according to medical experts, seems to be the third leading cause of death worldwide, after heart diseases and cancer. Diabetes is the third commonest cause of end stage renal failure in Nigeria."
"National prevalence of those living with diabetes, according to a national survey, is 2.2 per cent. That 2.3 in 100 people are suffering from diabetes. If considered in the light of our population of 140 million, the number of people who are already living with diabetes is considerably large. Also, a surveillance carried out in Lagos revealed that 3.2 per cent have diabetes in the urban areas because this is the place where sedentary lifestyle is prevalent."

"Type 2 diabetes accounts for 77.0 per cent of all cases of diabetes, type 1 diabetes 15.7 per cent, gestational diabetes 1.9 per cent and secondary diabetes 3.5 per cent. The increasing incidence of type 2 diabetes is demonstrated by the fact that in a survey done in Lagos in 1963, there were just five diabetic persons per 1000.

"Over time, diabetes can lead to blindness, kidney failure and nerve damage. These types of damage are the result of damage to small vessels, referred to as micro-vascular complications. Diabetes is also an important factor in accelerating the hardening and narrowing of the arteries (a theroscherosis), leading to strokes, coronary heart disease, and other complications. These complications, are referred to as macro-vascular complications.

"From experts point of view, proper nutrition is essential for anyone living with diabetes. Control of blood glucose levels is only one goal of a healthy eating plan for people with diabetes. A diet for those with diabetes should also help achieve and maintain a normal body weight as well as prevent heart and vascular diseases, which are frequent complications of diabetes.

"Medical practitioners and the pharmaceutical industry are rising to the challenge posed by diabetes, combining availability of effective drugs with education since education is power. Most of them have resolved to further inform both the masses and the people living with diabetes the causes of diabetes and its management.
"A good example of such efforts is the launch of Glucorance by Biofem Pharmaceutical Limited. Biotem is involved in the distribution of high quality pharmaceutical products for the treatment and monitoring of individuals living with type 2 diabetes mellitus.

"The company believes that little efforts, like facilitating such a gathering of experts could go a long way at forging better understanding of the peculiar nature of the disease in our environment.
"There has been a progressive increase in the incidence and prevalence of type 2 diabetes worldwide. This is particularly so especially in the underdeveloped and developing countries. This increase, of course, was brought about in changes in lifestyles as a result of urbanization and modernization, as well as genetic factors that are responsible for change. Such changes include changing from cultural to western nutrition habits, breastfeeding to artificial formulae, sedentary lifestyle and obesity.

"The relationship between lifestyle changes and type 2 diabetes has been explained by different hypothesis like the "thirty gene," poor ante-natal care, infant and childhood malnutrition. Experts believe that the genes which we get from our parents "load the gun" of type 2 diabetes, but the environment "pulls the trigger." So, a person may be genetically predisposed to diabetes, but lifestyle is what actually makes the individual become diabetic.

"There is no rigid prescribed diet plan for those with diabetes. Rather, eating plans are tailored to fit an individual needs, schedules, and eating habits. A diabetes diet plan must also be combined with the intake of appropriate diabetes medications. Glucovance promises to introduce a new dimension to diabetes medication.

"Glucovance, a fixed dose combination Metformin and Glibendamide is manufactured by Merck Sante, a multinational pharmaceutical company based in France and to already in use in several countries.
"In general, the principles of a healthy diabetes diet are the same for everyone. Consumption of a variety of foods, including whole grannies, fruits, non-fat dairy products, beans, and lean meats or vegetable substitutes, poultry and fish are recommended to achieve a healthy diet."

Reasons to call healthcare provider immediately

2008-11-24T07:48:00.000-08:00

* Signs of a life-threatening reaction. These include wheezing; tightness in the chest; fever; itching; bad cough; blue skin color; fits; swelling of face, lips, tongue, throat.
* Feeling very weak, tired, or uncomfortable.
* Unusual muscle pain, trouble breathing, stomach pain or discomfort, feeling cold, dizzy or lightheaded.
* Suddenly developing a slow or irregular heartbeat.
* Severe nausea, vomiting, fever, and/or diarrhea.
* Any signs or symptoms of infection. This may include a fever greater than 99 degrees, chills, sore throat, cough, increased sputum or change in color, painful urination, mouth sores, wound that will not heal, anal itching or pain.
* Low blood sugar or very high blood sugar.
* Any rash.

What should I monitor?

2008-11-24T07:47:00.001-08:00

* Check blood sugar as ordered by healthcare provider. Call if glucose is less than 80 mg/dL or greater than 250 mg/dL. Bring results to follow-up visits.
* Watch for low blood sugar. This can cause anger, shaking, rapid heartbeats, confusion, sweating.
* Watch for high blood sugar. Causes many trips to the bathroom, thirst, and weight loss.
* Check blood work for diabetes, kidney, and liver function. Talk with healthcare provider.
* Follow diet plan and exercise program as recommended by healthcare provider.
* Have a yearly eye exam and visit to the foot doctor.

Diabetes for Dummies

2008-11-24T07:46:00.000-08:00

When the first edition of Diabetes for Dummies came out in September 1999, I reviewed it and included it my my list of the 17 best books about diabetes. The second edition, just published by Wiley, is even better.

The author is Dr. Alan L. Rubin, an endocrinologist practicing in San Francisco. In the five years since he published the first edition of this book there have been huge advances in every phase of diabetes from diagnosis to diet. The second edition has all this and more. Some of the highlights to be found in this great book include:

* The newest blood glucose meters: the Accu-Chek Compact, the Ascensia Elite Diabetes Care System, the ExacTech RSG, GlucoWatch G2 Biographer, Hypoguard Advance, MiniMed Continuous Glucose Monitoring System, One Touch Ultra, Prestige LX, and others. Inexplicably, however, the book fails to mention my current favorite meters, TheraSense’s FreeStyle and FreeStyle Flash.

* The latest medications and combinations of medications including Glucovance, Glucophage XR, Glyset, Starlix, Avandamet as well as the latest information on Actos and Avandia. New insulins like NovoLog, Humalog, and Lantus. Using the old medications like Glucotrol, Micronase, and Glucophage to better control diabetes.

* Latest information on using Viagra and two newer drugs — Levitra and Cialis — to treat erectile dysfunction in men who have diabetes.

* The epidemic of type 2 diabetes in obese children and how to prevent it.

* Revisions in the diet for diabetes, the glycemic index, recommended calories and forbidden calories along with discussions of Atkins, South Beach, and other diets.

* The new 10,000 step exercise plan for diabetes with comments on other kinds of exercise and how exercise can prevent diabetes.

* New ideas about the psychology of diabetes including humorous stories from the thousands of people who have written to the author.

* New information on diabetes in Asians, African-Americans, and Hispanics, and the epidemic of obesity sweeping the world.

* New information on low blood glucose, plus how to avoid it and treat it when it occurs.

* New data on prevention of long-term complications like blindness and kidney failure.

* New advice for women who have diabetes and are pregnant or are postmenopausal, and those who wants to prevent pregnancy.

* New recommendations for the elderly population with diabetes.

* The revolution in providing insurance for and hiring people with diabetes.

* Cutting-edge information on future products and treatments that look promising.

* Hisses for products and treatments that rip off people with diabetes.

* Revisions of the websites (including mine) that provide the latest information on every aspect of diabetes.

The person who owns the first edition will want to be up-to-date and the person who has not bought the book yet will quickly decide there is a vast amount of information available in a readable, funny, and very positive form in the new second edition of Diabetes For Dummies. This 386-page softback book is available from fine bookstores everywhere for $21.99. Highly recommended.

Why It Is Used

2008-09-13T06:46:00.001-07:00

Sulfonylurea medications are prescribed when changes in diet, weight loss, and exercise do not keep the blood sugar level within a safe range. When taking one of these medications, it is still important to eat a balanced diet, exercise, and lose weight if needed.

These medications can help control blood sugar levels in children and young adults who have type 2 diabetes and are overweight.

Sulfonylurea medications are not safe if you:

* Are pregnant or trying to become pregnant. They may harm the fetus.
* Have liver or kidney problems. Sulfonylurea medications are broken down by the liver and pass out of the body through urine produced in the kidneys.

Tell your doctor if you have had a serious allergic reaction to a sulfa antibiotic, such as Bactrim or Septra. You may not be able to use a sulfonylurea.

How Well It Works

2008-09-13T06:45:00.003-07:00

Sulfonylurea medications work rapidly to control elevated blood sugar levels; they often are the first medication selected to treat people newly diagnosed with type 2 diabetes. Metformin is preferred for initial treatment because it doesn't cause low blood sugar or weight gain. The great majority of people have better control of their blood sugar by using a sulfonylurea medication along with diet and exercise than by using diet and exercise alone.

However, the medication may become less effective after several years of use. Some people who no longer respond to one sulfonylurea may respond to a different one.

Results of the United Kingdom Prospective Diabetes Study (UKPDS) showed that sulfonylurea medications:

* Were as effective as metformin and insulin in reducing blood sugar levels of people with type 2 diabetes.1
* Decreased the risk for complications of the eyes (retinopathy), kidneys (nephropathy), and nerves (neuropathy).2

Sulfonylurea medications do not decrease fat (triglycerides) in the blood as does metformin.

What To Think About

2008-09-13T06:45:00.001-07:00

Sulfonylurea medications are an effective treatment for many people with type 2 diabetes. If one of these medications keeps your blood sugar within a safe range, your risks of long-term complications of diabetes can be reduced. Other important factors that contribute to complications include high blood pressure, being overweight, high cholesterol levels, and smoking.

Few studies have been done on the use of oral medications for type 2 diabetes in children, and they have not been approved by the U.S. Food and Drug Administration (FDA) for use in children. But because these oral medications are safe for adults, most health professionals use them to treat children with type 2 diabetes.

Approval of FDA

2008-09-13T06:44:00.001-07:00

The first combination oral antihyperglycemic agent was recently approved by the Food and Drug Administration (FDA). Glucovance™, a combination of glyburide and metformin, is manufactured by Bristol-Myers Squibb. It is FDA-approved as first-line therapy for patients with Type 2 diabetes mellitus (DM) whose glucose is not controlled with diet and exercise. It can also be used as second-line therapy for patients whose blood glucose levels are not controlled with either a sulfonylurea or metformin alone.

Each individual component of Glucovance™ has its own unique mechanism of action. Glyburide, a sulfonylurea, lowers blood glucose by stimulating the pancreas to secrete insulin. Metformin, a biguanide, works by decreasing gluconeogenesis and intestinal glucose absorption, as well as enhancing insulin sensitivity.

Some common adverse effects associated with Glucovance™ include diarrhea, upper respiratory infection, lightheadedness, dizziness, shaking, hunger, and headache. Additionally, due to the metformin component, Glucovance™ may cause lactic acidosis, a rare but serious adverse effect. The risk of lactic acidosis increases with patient age and degree of renal insufficiency. To avoid lactic acidosis, it is recommended to 1) monitor renal function, 2) use the lowest dose possible of the metformin component, and 3) do not initiate its use in patients 80 years of age or older. Glucovance™ also has the potential to cause hypoglycemia because it stimulates insulin secretion. The risk is greatest in patients with decreased caloric intake, those taking concurrent glucose-lowering medications, or those ingesting alcohol.

Caution should be exercised when initiating or discontinuing agents that may cause hypoglycemia (e.g., nonsteroidal anti-inflammatory agents, warfarin, beta blockers) or hyperglycemia (e.g., diuretics, steroids, phenytoin, estrogens, calcium channel blockers) while patients are receiving Glucovance™. Drug interactions may also occur between metformin and agents that are excreted by renal tubular secretion (e.g., digoxin, procainamide, amiloride, quinidine, vancomycin).

Glucovance™ is contraindicated when serum creatinine levels are 1.5 mg/dL or higher in males or 1.4 mg/dL or higher in females, hypersensitivity to either component, kidney dysfunction, congestive heart failure, and acute or chronic metabolic acidosis.

If the patient's current combination therapy (e.g., glyburide [or another sulfonylurea] plus metformin) is changed to Glucovance™, the dose should not exceed the daily dose of sulfonylurea and metformin already being taken. See Table 1 for specific dosing recommendations of Glucovance™.

There are three tablet strengths of Glucovance™ available: 1.25 mg/250 mg (glyburide/metformin), 2.5 mg/500 mg, and 5 mg/500 mg. Based on the average wholesale price (AWP), the costs are approximately $0.66, $0.78, and $0.78 per tablet, respectively.

There are advantages for combining glyburide and metformin: 1) lower doses are required for glucose control, 2) fewer adverse effects may occur, and 3) increase in patient acceptance and compliance. In addition, patients should maintain a good diet and exercise program, as well as regular blood glucose monitoring.

Recommended dosage

2008-08-31T08:14:00.000-07:00

ADULTS

Your doctor will start therapy at a low dose and increase it until your blood sugar levels are under control.

For patients not previously treated with diabetes medications

The recommended starting dose is 1.25 milligrams of glyburide with 250 milligrams of metformin once or twice daily with meals. The dosage can be increased every two weeks until blood sugar levels are controlled. The maximum recommended daily dosage of Glucovance for previously untreated patients is 10 milligrams of glyburide with 2,000 milligrams of metformin.

For patients previously treated with glyburide (or a similar drug) or metformin:

The recommended starting dose of Glucovance is either 2.5 or 5 milligrams of glyburide with 500 milligrams of metformin twice daily with meals. The maximum recommended daily dosage of Glucovance for previously treated patients is 20 milligrams of glyburide with 2,000 milligrams of metformin.

CHILDREN

Glucovance is not for use in children.

OLDER ADULTS

Since kidney function declines with age, it should be closely monitored in people taking Glucovance after age 65. Older patients are usually not prescribed the maximum recommended dose of Glucovance.

Glucovance Drug Interactions Explained

2008-08-31T08:13:00.001-07:00

Beta Blockers
Taking Glucovance with beta blockers can increase your risk of low blood sugar (hypoglycemia). If you are taking Glucovance along with a beta blocker, you may need to be monitored more closely, and your healthcare provider may need to adjust your Glucovance dose -- especially when you are starting or stopping a beta blocker.

Calcium Channel Blockers
Taking Glucovance with calcium channel blockers can make Glucovance less effective, increasing your chance of high blood sugar (hyperglycemia). If you are taking these medicines together, you may need to be monitored more closely, and your healthcare provider may need to adjust your Glucovance dose -- especially when you are starting or stopping a calcium channel blocker.

Certain Decongestants
Taking Glucovance with certain decongestants can make Glucovance less effective, increasing your chance of high blood sugar (hyperglycemia). Decongestants are in many cough and cold products, so be sure to talk with your healthcare provider before taking any of these products.

Cimetidine (Tagamet)
Taking Glucovance with cimetidine can increase the level of Glucovance in your blood, increasing your risk of side effects. Your healthcare provider may need to adjust your dose of these medications or may suggest an alternative to cimetidine.

Corticosteroids
Taking Glucovance with corticosteroids can make Glucovance less effective, increasing your chance of high blood sugar (hyperglycemia). If you are taking these drugs together, you may need to be monitored more closely, and your healthcare provider may need to adjust your Glucovance dose -- especially when you are starting or stopping a corticosteroid.

Symptoms of a Glucovance Overdose

2008-08-31T08:12:00.002-07:00

The effects of a Glucovance overdose may include:
* Low blood sugar (hypoglycemia)
* Lactic acidosis, due to the metformin component of Glucovance (see Metformin and Lactic Acidosis).

Possible symptoms of low blood sugar include:

* Sweating
* Shakiness
* Extreme hunger
* Dizziness
* Cold sweats
* Blurry vision.

More severe low blood sugar symptoms include:

* Changes in behavior, such as irritability
* Loss of coordination
* Difficulty speaking
* Confusion
* Seizures
* Loss of consciousness
* Coma
* Loss of life.

Lactic acidosis symptoms include:

* Feeling tired or weak
* Muscle pain
* Trouble breathing
* Abdominal pain (or stomach pain)
* Feeling cold
* Dizziness or lightheadedness
* A slow or irregular heartbeat
* Loss of life.

On-line Medication Resources

2008-08-31T08:12:00.001-07:00

* Drugs.com is a new Internet drug information resource. You have to register, but it's free. Drugs.com gets its main database and Care Guide information from Micromedex, a part of the global Thomson Health Care Information group. The Drug Interactions information comes from Multum Information Services, a company that specializes in solutions to the growing problem of adverse drug events. A pharmacist at Drugs.com tells me that the site contains about 24,000 drug names. It unfortunately has an interface that makes entering more than a few items tedious. The URL is
http://www.drugs.com/

* Drugstore.com has an excellent and easy-to-use drug interaction tool, albeit one that is hard to find. The URL is Drug Interactions

* The Express Scripts “Check Interactions” site is http://www.drugdigest.org/DD/Interaction/ChooseDrugs/1,4109,,00.html.

* Another drug interaction site is Discovery Health’s “Drug Interaction Checker.” The URL of this tool is http://health.discovery.com/encyclopedias/checker/checker.jsp.

* The Diabetes Monitor: Medications has many links to Web sites about diabetes medications. The URL is
http://www.diabetesmonitor.com/other-05.htm

* RxList - The Internet Drug Index is a free, searchable database of more than 4,500 prescription and over-the-counter medications. The search engine uses fuzzy logic, so you can often find a drug even when you misspell its name. The URL is
http://www.rxlist.com/

* Healthtouch® Drug Information enables you to find information about more than 10,000 prescription and over-the-counter medications. You can enter either the generic or brand name of the drug, but you have to spell it correctly. While it includes more drugs than RxList, the information it provides is less detailed. The URL is
http://www.healthtouch.com/level1/p_dri.htm

* Johns Hopkins IntelliHealth lets you search its U. S. Pharmacopeia database for drug information. The URL is
http://www.intelihealth.com/email/drugs

Possible food and drug interactions

2008-08-31T08:11:00.001-07:00

If Glucovance is taken with certain other drugs, the effects of either drug could be increased, decreased, or altered. It is especially important to check with your doctor before combining Glucovance with the following:

Airway-opening drugs such as Proventil and Ventolin
Beta-blockers (heart and blood-pressure drugs such as Inderal and Tenormin)
Birth control pills
Calcium channel blockers (heart medications) such as Calan, Isoptin, and Procardia
Chloramphenicol (Chloromycetin)
Ciprofloxacin (Cipro)
Estrogens such as Premarin
HydroDiuril, Lasix, and other diuretics
Isoniazid (Rifamate)
Major tranquilizers such as Compazine, Stelazine, and Thorazine
MAO inhibitors such as the antidepressants Nardil and Parnate
Nonsteroidal anti-inflammatory drugs such as Advil, Motrin, Naprosyn, and Voltaren
Niacin (Niacor, Niaspan)
Phenytoin (Dilantin)
Probenecid
Steroids such as prednisone (Deltasone)
Sulfa drugs such as Bactrim
Thyroid medications such as Synthroid
Warfarin (Coumadin)

Special warnings

2008-08-31T08:08:00.000-07:00

About Glucovance

Avoid excessive alcohol intake while taking Glucovance. Heavy drinking increases the danger of lactic acidosis and can also trigger an attack of low blood sugar (hypoglycemia).

Missed meals, malnutrition, general debility, liver or kidney problems, other medications, and over-exertion also increase the risk of hypoglycemia. Symptoms of a mild case include cold sweats, dizziness, shakiness, and hunger. Severe hypoglycemia can lead to seizures and coma. If you notice any of the warning signs, check with your doctor immediately.

Lactic acidosis also becomes more likely when you become dehydrated. If you experience severe vomiting, diarrhea, fever, or if your fluid intake is significantly reduced, tell your doctor.

Taking Glucovance with certain diabetes drugs, such as Avandia, can increase the risk of hypoglycemia, weight gain, and liver problems. Your doctor will periodically test your liver function to guard against any problems.

Glucovance occasionally causes a mild deficiency of vitamin B12. Your doctor will check annually and may prescribe a supplement if necessary.

Some experts suspect that the glyburide component of Glucovance may lead to more heart problems than treatment with diet alone. In a long-term trial of a similar drug, researchers noted an increase in heart-related deaths (though the overall mortality rate remained unchanged). If you have a heart condition, you may want to discuss this potential risk with your doctor.

Note It

2008-08-23T21:40:00.000-07:00

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Medication Look Like

2008-08-23T21:39:00.000-07:00

Glyburide and metformin is available with a prescription under the brand name Glucovance. Other brand or generic formulations may also be available. Ask your pharmacist any questions you have about this medication, especially if it is new to you.

* Glucovance 1.25 mg glyburide/250 mg metformin--pale yellow, capsule-shaped, film-coated tablets
* Glucovance 2.5 mg glyburide/500 mg metformin--pale orange, capsule-shaped, film-coated tablets
* Glucovance 5 mg glyburide/500mg metformin-- yellow, capsule-shaped, film-coated tablets

Sulfonylureas for type 2 diabetes

2008-08-21T06:13:00.000-07:00

Examples
Generic Name Brand Name
glimepiride Amaryl
glipizide Glucotrol
glipizide and metformin Metaglip
glyburide DiaBeta, Glynase, Micronase
glyburide and metformin hydrochloride Glucovance

Most sulfonylurea medications for type 2 diabetes can be taken once a day. Some need to be taken twice a day.

These medications work for a long time and can cause low blood sugar. It is very important not to skip or delay meals when taking these medications.

Glucovance is a combination medication that contains glyburide and metformin hydrochloride, a biguanide.

Metaglip is a combination medication that contains glipizide and metformin.
How It Works

Sulfonylurea medications:

* Increase the amount of insulin produced by the pancreas. This is the primary action of these medications.

Because Glucovance and Metaglip are combination medications that contain metformin, they decrease the amount of sugar your liver makes and may increase your body's ability to respond to insulin.
Why It Is Used

Sulfonylurea medications are prescribed when changes in diet, weight loss, and exercise do not keep the blood sugar level within a safe range. When taking one of these medications, it is still important to eat a balanced diet, exercise, and lose weight if needed.

These medications can help control blood sugar levels in children and young adults who have type 2 diabetes and are overweight.

Sulfonylurea medications are not safe if you:

* Are pregnant or trying to become pregnant. They may harm the fetus.
* Have liver or kidney problems. Sulfonylurea medications are broken down by the liver and pass out of the body through urine produced in the kidneys.

Tell your doctor if you have had a serious allergic reaction to a sulfa antibiotic, such as Bactrim or Septra. You may not be able to use a sulfonylurea.
How Well It Works

Sulfonylurea medications work rapidly to control elevated blood sugar levels; they often are the first medication selected to treat people newly diagnosed with type 2 diabetes. Metformin is preferred for initial treatment because it doesn't cause low blood sugar or weight gain. The great majority of people have better control of their blood sugar by using a sulfonylurea medication along with diet and exercise than by using diet and exercise alone.

However, the medication may become less effective after several years of use. Some people who no longer respond to one sulfonylurea may respond to a different one.

Results of the United Kingdom Prospective Diabetes Study (UKPDS) showed that sulfonylurea medications:

* Were as effective as metformin and insulin in reducing blood sugar levels of people with type 2 diabetes.1
* Decreased the risk for complications of the eyes (retinopathy), kidneys (nephropathy), and nerves (neuropathy).2

Sulfonylurea medications do not decrease fat (triglycerides) in the blood as does metformin.
Side Effects

Side effects are uncommon when sulfonylureas are taken as prescribed. Low blood sugar is the most common side effect. The risk of very low blood sugar is greater with medications that work longer in the body.

Drinking alcohol increases the risk of a low blood sugar level if you take a sulfonylurea medication. If you drink alcohol, limit yourself to only 1 to 2 drinks per day and eat something before you drink alcohol.

Sulfonylurea medications can cause weight gain. They also tend to keep insulin levels in the body high for long periods of time. Over time, high levels of insulin (hyperinsulinemia) may increase your chances of getting heart disease.

Blood levels of vitamin B12 can decrease in some people who take metformin.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)
What To Think About

Sulfonylurea medications are an effective treatment for many people with type 2 diabetes. If one of these medications keeps your blood sugar within a safe range, your risks of long-term complications of diabetes can be reduced. Other important factors that contribute to complications include high blood pressure, being overweight, high cholesterol levels, and smoking.

Few studies have been done on the use of oral medications for type 2 diabetes in children, and they have not been approved by the U.S. Food and Drug Administration (FDA) for use in children. But because these oral medications are safe for adults, most health professionals use them to treat children with type 2 diabetes.

Dosage

2008-08-21T06:12:00.000-07:00

Adults: Oral:

Initial therapy (no prior treatment with sulfonylurea or metformin): 1.25 mg/250 mg once daily with a meal; patients with Hb A1c >9% or fasting plasma glucose (FPG) >200 mg/dL may start with 1.25 mg/250 mg twice daily

Dosage may be increased in increments of 1.25 mg/250 mg, at intervals of not less than 2 weeks; maximum daily dose: 10 mg/2000 mg (limited experience with higher doses)

Previously treated with a sulfonylurea or metformin alone: Initial: 2.5 mg/500 mg or 5 mg/500 mg twice daily; increase in increments no greater than 5 mg/500 mg; maximum daily dose: 20 mg/2000 mg

When switching patients previously on a sulfonylurea and metformin together, do not exceed the daily dose of glyburide (or glyburide equivalent) or metformin.

Note: May combine with a thiazolidinedione in patients with an inadequate response to glyburide/metformin therapy (risk of hypoglycemia may be increased).

Elderly: Oral: Conservative doses are recommended in the elderly due to potentially decreased renal function; do not titrate to maximum dose; should not be used in patients 80 years of age unless renal function is verified as normal

Dosage adjustment in renal impairment: Risk of lactic acidosis increases with degree of renal impairment; contraindicated in renal disease or renal dysfunction (see Contraindications)

Dosage adjustment in hepatic impairment: Use conservative initial and maintenance doses and avoid use in severe hepatic disease
Note: Dose must be individualized. Dosages expressed as glyburide/metformin components.

Dietary Considerations

2008-08-21T06:11:00.000-07:00

May cause GI upset; take with food to decrease GI upset. Dietary modification based on ADA recommendations is a part of therapy. Decreases blood glucose concentration. Hypoglycemia may occur. Must be able to recognize symptoms of hypoglycemia (palpitations, sweaty palms, lightheadedness). Monitor for signs and symptoms of vitamin B12 deficiency. Monitor for signs and symptoms of folic acid deficiency.

Glucovance FDA approval

2008-08-21T06:03:00.000-07:00

GlyBURIDE

2008-08-14T08:24:00.000-07:00

Drug Information Provided by Lexi-Comp

This information has been developed and provided by an independent third-party source. Merck & Co., Inc. does not endorse and is not responsible for the accuracy of the content, or for practices or standards of non-Merck sources.

Medication Safety Issues

Sound-alike/look-alike issues:

GlyBURIDE may be confused with glipiZIDE, Glucotrol®

Dia?eta® may be confused with Diabinese®, Zebeta®

Micronase® may be confused with microK®, miconazole, Micronor®, Microzide™

High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Pronunciation

(GLYE byoor ide)

U.S. Brand Names

* Dia?eta®
* Glynase® PresTab®
* Micronase®

Index Terms

* Diabeta
* Glibenclamide
* Glybenclamide
* Glybenzcyclamide

Generic Available

Yes

Canadian Brand Names

* Albert® Glyburide
* Apo-Glyburide®
* Dia?eta®
* Euglucon®
* Gen-Glybe
* Novo-Glyburide
* Nu-Glyburide
* PMS-Glyburide
* ratio-Glyburide
* Sandoz-Glyburide

Pharmacologic Category

*
Antidiabetic Agent, Sulfonylurea

Pharmacologic Category Synonyms

* Oral Hypoglycemic Agent, Sulfonylurea
* Sulfonylurea

Use

Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM)

Use: Unlabeled/Investigational

Alternative to insulin in women for the treatment of gestational diabetes (11-33 weeks gestation)

Pregnancy Risk Factor

B/C (manufacturer dependent)

Pregnancy Implications

Glyburide was not found to significantly cross the placenta in vitro and was not found in the cord serum infants of mothers taking glyburide for gestational diabetes mellitus (GDM). Reported teratogenic effects may be due to poorly controlled maternal diabetes; abnormal blood glucose levels in the mother are associated with a higher incidence of congenital abnormalities. Nonteratogenic effects such as hypoglycemia in the neonate have been associated with maternal glyburide use. The manufacturer recommends that if glyburide is used during pregnancy, it should be discontinued at least 2 weeks before the expected delivery date. Although studies have shown positive outcomes using glyburide for the treatment of GDM, use may not be appropriate for all women. When compared to insulin for the treatment of GDM, as the severity of GDM increased, the success rate of treatment decreased. It should be noted that studies using glyburide for the treatment of GDM have initiated treatment after the period of organogenesis. Insulin is considered the drug of choice for the control of diabetes mellitus during pregnancy.Reproduction studies differ by manufacturer labeling. Because adverse events were not observed in animal reproduction studies, one manufacturer classifies glyburide as pregnancy category B. Because adverse events were noted in animal studies during the period of lactation, another manufacturer classifies glyburide as pregnancy category C.

Lactation

Does not enter breast milk/ use caution

Breast-Feeding Considerations

Data from initial studies note that glyburide was not detected in breast milk. Breast-feeding is not recommended by the manufacturer. Potentially, hypoglycemia may occur in a nursing infant exposed to a sulfonylurea via breast milk.

Contraindications

Hypersensitivity to glyburide, any component of the formulation, or other sulfonamides; type 1 diabetes mellitus (insulin dependent, IDDM), diabetic ketoacidosis; concurrent use with bosentan

Warnings/Precautions

Concerns related to adverse reactions:

• Cardiovascular mortality: Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS) have not supported an association.

• Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used. It is also more likely in elderly patients, malnourished patients and in patients with impaired renal, hepatic, adrenal and/or pituitary function; use with caution.

• Sulfonamide allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.

Disease-related concerns:

• Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).

Special populations:

• Elderly: Rapid and prolonged hypoglycemia (>12 hours) despite hypertonic glucose injections have been reported; age and hepatic and renal impairment are independent risk factors for hypoglycemia; dosage titration should be made at weekly intervals.

• Pediatrics: Safety and efficacy have not been established in children.

Adverse Reactions

Frequency not defined.

Cardiovascular: Vasculitis

Central nervous system: Headache, dizziness

Dermatologic: Erythema, maculopapular eruptions, morbilliform eruptions, pruritus, purpura, rash, urticaria, photosensitivity reaction

Endocrine & metabolic: Disulfiram-like reaction, hypoglycemia, hyponatremia (SIADH reported with other sulfonylureas)

Gastrointestinal: Nausea, epigastric fullness, heartburn, constipation, diarrhea, anorexia

Genitourinary: Nocturia

Hematologic: Leukopenia, thrombocytopenia, hemolytic anemia, agranulocytosis, aplastic anemia, pancytopenia, porphyria cutanea tarda

Hepatic: Cholestatic jaundice, hepatitis, transaminase increased

Neuromuscular & skeletal: Arthralgia, myalgia, paresthesia

Ocular: Blurred vision

Renal: Diuretic effect (minor)

Miscellaneous: Allergic reaction

Drug Interactions

Inhibits CYP2C8 (weak), 3A4 (weak)

Beta-blockers: Beta-blockers may enhance the hypoglycemic effect of glyburide and mask tachycardia as an initial symptom of hypoglycemia.

Bosentan: Glyburide may enhance the hepatotoxic effect and increase the metabolism of bosentan. Bosentan may increase the metabolism of glyburide. Concomitant use is contraindicated

Chloramphenicol: Chloramphenicol may decrease the metabolism of glyburide.

Cimetidine: Cimetidine may decrease the metabolism, via CYP isoenzymes, of glyburide.

Cyclic antidepressants: Cyclic antidepressants may enhance the hypoglycemic effect of glyburide.

Cyclosporine: Glyburide may increase the serum concentration of cyclosporine.

Fibric acid derivatives: Fibric acid derivatives may enhance the hypoglycemic effect of glyburide.

Fluconazole: Fluconazole may increase the serum concentration of glyburide.

Pegvisomant: Pegvisomant may enhance the hypoglycemic effect of glyburide.

Quinolone antibiotics: Quinolone antibiotics may enhance the hypoglycemic effect of glyburide.

Rifampin: Rifampin may increase the metabolism, via CYP isoenzymes, of glyburide.

Salicylates: Salicylates may enhance the hypoglycemic effect of glyburide. Of concern with regular, higher doses of salicylates, not sporadic, low doses.

Sulfonamide derivatives (sulfadiazine, sulfadoxine, sulfamethoxazole, sulfisoxazole): Sulfonamide derivatives (except sulfacetamide) may enhance the hypoglycemic effect of glyburide.

Ethanol/Nutrition/Herb Interactions

Ethanol: Caution with ethanol (may cause hypoglycemia).

Herb/Nutraceutical: Herbs with hypoglycemic properties may enhance the hypoglycemic effect of glyburide. This includes alfalfa, aloe, bilberry, bitter melon, burdock, celery, damiana, fenugreek, garcinia, garlic, ginger, ginseng (American), gymnema, marshmallow, stinging nettle

Mechanism of Action

Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites

Pharmacodynamics/Kinetics

Onset of action: Serum insulin levels begin to increase 15-60 minutes after a single dose

Duration: ?24 hours

Absorption: Significant within 1 hour

Distribution: 9-10 L

Protein binding, plasma: >99% primarily to albumin

Metabolism: Hepatic; forms metabolites (weakly active)

Half-life elimination: Diabeta®, Micronase®: 10 hours; Glynase® PresTab®: ?4 hours; may be prolonged with renal or hepatic impairment

Time to peak, serum: Adults: 2-4 hours

Excretion: Feces (50%) and urine (50%) as metabolites

Dosage

Oral: Adults:

Dia?eta®, Micronase®:

Initial: 2.5-5 mg/day, administered with breakfast or the first main meal of the day. In patients who are more sensitive to hypoglycemic drugs, start at 1.25 mg/day.

Increase in increments of no more than 2.5 mg/day at weekly intervals based on the patient's blood glucose response

Maintenance: 1.25-20 mg/day given as single or divided doses; maximum: 20 mg/day

Elderly: Initial: 1.25-2.5 mg/day, increase by 1.25-2.5 mg/day every 1-3 weeks

Micronized tablets (Glynase® PresTab®): Adults:

Initial: 1.5-3 mg/day, administered with breakfast or the first main meal of the day in patients who are more sensitive to hypoglycemic drugs, start at 0.75 mg/day. Increase in increments of no more than 1.5 mg/day in weekly intervals based on the patient's blood glucose response.

Maintenance: 0.75-12 mg/day given as a single dose or in divided doses. Some patients (especially those receiving >6 mg/day) may have a more satisfactory response with twice-daily dosing. Maximum: 12 mg/day

Dosing adjustment/comments in renal impairment: Clcr <50 mL/minute: Not recommended

Dosing adjustment in hepatic impairment: Use conservative initial and maintenance doses and avoid use in severe disease

Administration: Oral

Administer with meals at the same time each day. Patients who are anorexic or NPO may need to have their dose held to avoid hypoglycemia.

Monitoring Parameters

Signs and symptoms of hypoglycemia, fasting blood glucose, hemoglobin A1c

Reference Range

Recommendations for glycemic control in adults with diabetes:

Hb A1c: <7%

Preprandial capillary plasma glucose: 70-130 mg/dL

Peak postprandial capillary blood glucose: <180 mg/dL

Blood pressure: <130/80 mm Hg

Dietary Considerations

Should be taken with meals at the same time each day. Dietary modification based on ADA recommendations is a part of therapy. Decreases blood glucose concentration. Hypoglycemia may occur. Must be able to recognize symptoms of hypoglycemia (palpitations, sweaty palms, lightheadedness).

Patient Education

Do not take any new medication during therapy unless approved by prescriber. This medication is used to control diabetes; it is not a cure. Monitor glucose as recommended by prescriber. Other important components of treatment plan may include prescribed diet and exercise regimen (consult prescriber or diabetic educator). If you experience hypoglycemic reaction, contact prescriber immediately. Always carry quick source of sugar with you. Take exactly as directed, 30 minutes before meal(s) at the same time each day. Do not change dose or discontinue without consulting prescriber. Avoid alcohol while taking this medication; could cause severe reaction. Do not take other medication within 2 hours of this medication unless advised by prescriber. You may experience more sensitivity to sunlight (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); headache; or nausea (consult prescriber if these persist). Report severe or persistent side effects; hypoglycemia (palpitations, sweaty palms, lightheadedness); extended vomiting, diarrhea, or constipation; flu-like symptoms; skin rash; easy bruising or bleeding; or change in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Do not breast-feed.

Geriatric Considerations

Rapid and prolonged hypoglycemia (>12 hours) despite hypertonic glucose injections has been reported; age, hepatic, and renal impairment are independent risk factors for hypoglycemia; dosage titration should be made at weekly intervals. How “tightly” a geriatric patient's blood glucose should be controlled is controversial; however, a fasting blood sugar <150 mg/dL is now an acceptable endpoint. Such a decision should be based on the patient's functional and cognitive status, how well they recognize hypoglycemic or hyperglycemic symptoms, and how to respond to them and their other disease states. Use with caution in the elderly with renal insufficiency.

Anesthesia and Critical Care Concerns/Other Considerations

The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.

Cardiovascular Considerations

The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. However, there are presently only limited data to support this premise, particularly with newer generation agents. An early study suggested poor cardiovascular outcomes in patients with diabetes treated with tolbutamide. Retrospective studies evaluating cardiovascular outcomes following angioplasty and acute myocardial infarction in patients with diabetes receiving newer sulfonylureas are inconsistent. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.

Dental Health: Effects on Dental Treatment

Glyburide-dependent patients with diabetes (noninsulin dependent, type 2) should be appointed for dental treatment in morning in order to minimize chance of stress-induced hypoglycemia.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Dizziness is common

Mental Health: Effects on Psychiatric Treatment

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; phenothiazines and TCAs may antagonize glimepiride hypoglycemic effects; MAO inhibitors and TCAs may enhance hypoglycemic effects

Nursing: Physical Assessment/Monitoring

Assess allergy history prior to beginning therapy. Assess potential for interactions with other prescriptions, OTC medications, or herbal products patient may be taking. Assess results of laboratory tests, therapeutic effectiveness, and adverse response (eg, hypoglycemia) at regular intervals during therapy. Teach patient proper use (or refer patient to diabetic educator) for instruction, possible side effects/appropriate interventions, and adverse symptoms to report.

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet: 1.25 mg, 2.5 mg, 5 mg

Dia?eta®, Micronase®: 1.25 mg, 2.5 mg, 5 mg

Tablet, micronized: 1.5 mg, 3 mg, 6 mg

Glynase® PresTab®: 3 mg, 6 mg

Pricing: U.S. (www.drugstore.com)

Tablets (Diabeta)

1.25 mg (50): $27.11

2.5 mg (30): $28.20

5 mg (30): $35.99

Tablets (GlyBURIDE)

1.25 mg (30): $12.99

2.5 mg (30): $12.99

5 mg (30): $11.99

Tablets (GlyBURIDE Micronized)

1.5 mg (60): $16.00

3 mg (60): $20.99

6 mg (60): $33.99

Tablets (Glynase)

1.5 mg (60): $47.69

3 mg (60): $70.13

6 mg (60): $109.42

Tablets (Micronase)

1.25 mg (30): $17.39

2.5 mg (30): $28.10

5 mg (30): $44.99

References

ACOG Practice Bulletin, Clinical Management Guidelines for Obstetrician-Gynecologists, Number 60, March 2005, "Pregestational Diabetes Mellitus," Obstet Gynecol , 2005, 105(3):675-85.

American Diabetes Association, “Standards of Medical Care in Diabetes Mellitus - 2008,” Diabetes Care, 2008, 30(Suppl 1):12-54.

“A Study of the Effects of Hypoglycemia Agents on Vascular Complications in Patients With Adult-onset Diabetes. VI. Supplementary Report on Nonfatal Events in Patients Treated With Tolbutamide. The University Group Diabetes Program,” Diabetes, 1976, 25(12):1129-53.

Brodows RG, “Benefits and Risks With Glyburide and Glipizide in Elderly NIDDM Patients,” Diabetes Care, 1992, 15(1):75-80.

“Effect of Intensive Blood-Glucose Control With Metformin on Complications in Overweight Patients With Type 2 Diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):854-65.

Elliott BD, Schenker S, Langer O, et al, "Comparative Placental Transport of Oral Hypoglycemic Agents in Humans: A Model of Human Placental Drug Transfer," Am J Obstet Gynecol, 1994, 171(3):653-60.

Feig DS, Briggs GG, Kraemer JM, et al, "Transfer of Glyburide and Glipizide Into Breast Milk," Diabetes Care, 2005, 28(8):1851-5.

Gabbe SG and Graves CR, "Management of Diabetes Mellitus Complicating Pregnancy," Obstet Gynecol, 2003, 102(4):857-68.

Garratt KN, Brady PA, Hassinger NL, et al, “Sulfonylurea Drugs Increase Early Mortality in Patients With Diabetes Mellitus After Direct Angioplasty for Acute Myocardial Infarction,” J Am Coll Cardiol, 1999, 33(1):119-24.

Gavin JR 3d, “Glyburide: New Insights Into Its Effects on the Beta Cell and Beyond - Introduction,” Am J Med, 1990, 89(2A):1S-2S.

“Intensive Blood-Glucose Control With Sulphonylureas or Insulin Compared With Conventional Treatment and Risk of Complications in Patients With Type 2 Diabetes (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group,” Lancet, 1998, 352(9131):837-53.

Jacobson GF, Ramos GA, Ching JY, et al, "Comparison of Glyburide and Insulin for the Management of Gestational Diabetes in a Large Managed Care Organization," Am J Obstet Gynecol, 2005, 193(1):118-24.

Klamann A, Sarfert P, Launhardt V, et al, “Myocardial Infarction in Diabetic vs Nondiabetic Subjects. Survival and Infarct Size Following Therapy With Sulfonylureas (Glibenclamide),” Eur Heart J, 2000, 21(3):220-9.

Langer O, Conway D, Berkus M, et al, “A Comparison of Glyburide and Insulin in Women With Gestational Diabetes Mellitus,” N Engl J Med, 2000, 343(16):1134-8.

Langer O, Yogev Y, Xenakis EM, et al, "Insulin and Glyburide Therapy: Dosage, Severity Level of Gestational Diabetes, and Pregnancy Outcome," Am J Obstet Gynecol , 2005, 192(1):134-9.

Meinert CL, Knatterud GL, Prout TE, et al, “A Study of the Effects of Hypoglycemic Agents on Vascular Complications in Patients With Adult-Onset Diabetes. II. Mortality Results,” Diabetes, 1970, 19:789-830.

Nadel HL, “Formulary Conversion From Glipizide to Glyburide: A Cost-Minimization Analysis,” Hosp Pharm, 1995, 30:472-74.

Nataas OB and Nesthus I, “Immune Haemolytic Anaemia Induced by Glibenclamide in Selective IgA Deficiency,” Br Med J (Clin Res Ed), 1987, 295(6594):366-7.

O'Keefe JH, Blackstone EH, Sergeant P, et al, “The Optimal Mode of Coronary Revascularization for Diabetics. A Risk-Adjusted Long-Term Study Comparing Coronary Angioplasty and Coronary Bypass Surgery,” Eur Heart J, 1998, 19(11):1696-703.

Pearson JG, “Pharmacokinetics of Glyburide,” Am J Med, 1985, 79(3B):67-71.

Rosenstock J, Corrao PJ, Goldberg RB, et al, “Diabetes Control in the Elderly: A Randomized, Comparative Study of Glyburide Versus Glipizide in Noninsulin-Dependent Diabetes Mellitus,” Clin Ther, 1993, 15(6):1031-40.

Schwinghammer TL, Antal EJ, Kubacka RT, et al, “Pharmacokinetics and Pharmacodynamics of Glyburide in Young and Elderly Nondiabetic Adults,” Clin Pharm, 1991, 10(7):532-8.

Sillence DO and Court JM, “Glibenclamide-Induced Hypoglycemia,” Br Med J, 1975, 3(5981):490-1.

Sonnenblick M and Shilo S, “Glibenclamide Induced Prolonged Hypoglycaemia,” Age Ageing, 1986, 15(3):185-9.

International Brand Names

* Amecladin (PH)
* Apo-Glibenclamide (NZ)
* Benclamin (TH)
* Betanase (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Betanese 5 (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Bevoren (LU)
* Calabren (CZ)
* Clamide (HK)
* Daonil (AE, AR, AU, BB, BD, BE, BF, BH, BJ, BM, BO, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, DK, DO, EC, EG, ET, FR, GB, GH, GM, GN, GR, GT, GY, HK, HN, HR, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, NO, NZ, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SG, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW)
* Daono (TH)
* Debtan (TH)
* Diaben (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Diabitor (PH)
* Dibelet (MY, TH)
* Euclamin (PL)
* Euglucan (FR)
* Euglucon (AE, AR, AT, AU, BB, BD, BE, BF, BH, BJ, BM, BO, BR, BS, BZ, CH, CI, CL, CN, CO, CR, CY, CZ, DE, DO, EC, EG, ES, ET, FI, GH, GM, GN, GR, GT, GY, HK, HN, HR, ID, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KP, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, OM, PA, PE, PH, PK, PR, PT, PY, QA, RU, SA, SC, SD, SE, SG, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW)
* Euglusid (CN)
* Gilemal (AT, BG, HN, HU)
* Gliban (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Glibedal (HR)
* Gliben (IT, NZ)
* Glibenclamid (HR)
* Glibenclamid Pharmavit (HU)
* Glibenclamid-ratiopharm (LU)
* Glibenhexal (LU)
* Glibens (CO)
* Glibesyn (MY, SG)
* Glibet (IN)
* Glibetic (IL)
* Glibil (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE)
* Gliboral (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Glidiabet (PE)
* Glimel (AU, HK, SG)
* Glimide (MY)
* Glisulin (KP)
* Glitisol (BB, BM, BS, BZ, GY, HK, JM, NL, SR, TT)
* Gluben (IL)
* Glucal (MX)
* Glucobene (HU)
* Glucomid (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW)
* Gluconic (ID)
* Glulo (ID)
* Glyamid (ID)
* Glycomin (ZA)
* Glynase (BB, BM, BS, BZ, GY, JM, NL, SR, TT)
* Hemi-Daonil (AR, FR, MA, NL)
* Insol (PH)
* Lodulce (PH)
* Maninil (EE, PL)
* Manoglucon (TH)
* Melix (AE, BB, BF, BH, BJ, BM, BS, BZ, CI, CY, EG, ET, GH, GM, GN, GY, IL, IQ, IR, JM, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, NE, NG, NL, OM, QA, SA, SC, SD, SL, SN, SR, SY, TN, TT, TZ, UG, YE, ZA, ZM, ZW)
* Miglucan (FR)
* Norboral (MX)
* Norglicem (ES)
* Orabetic (PH)
* Pira (AR)
* Renabetic (ID)
* Semi-Daonil (AE, AR, AU, BH, CH, CY, EG, GB, HK, ID, IE, IL, IQ, IR, JO, KW, LB, LY, MA, NZ, OM, PT, QA, SA, SY, YE)
* Semi-Euglucon (AR, AT, AU, NL, PH, TH)
* Sugril (TH)
* Tiabet (ID)
* Trodeb (ID)
* Unil-5 (TH)
* Xeltic (HK)

Glucovance Oral Uses

2008-08-14T08:23:00.001-07:00

Glyburide is an anti-diabetic drug (sulfonylurea-type) used along with a proper diet and exercise program to control high blood sugar. It is used in patients with type 2 diabetes (non-insulin-dependent diabetes). It works by stimulating the release of your body's natural insulin. Effectively controlling high blood sugar helps prevent heart disease, strokes, kidney disease, blindness, and circulation problems, as well as sexual function problems (impotence).
How to use Glyburide Oral

Take this medication by mouth with breakfast or the first main meal, usually once daily; or use as directed by your doctor. Some patients, especially those taking higher doses, may be directed to take this drug twice a day. The dosage is based on your medical condition and response to therapy.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time(s) each day. Monitor blood glucose levels on a regular basis. Inform your doctor if your blood glucose measurements are too high or too low.

GLUCOVANCE - Drug Description

2008-08-14T08:22:00.003-07:00

GLUCOVANCE® (Glyburide and Metformin HCl Tablets) contains two oral antihyper-glycemic 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-cyclo-hexylurea. Glyburide is a white to off-white crystalline compound with a molecular formula of C23H28ClN3O5S 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. The structural formula is represented below.

GLUCOVANCE® (Glyburide and Metformin HCl Tablets) Structural Formula Illustration

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 α-glucosidase inhibitors. It is a white to off-white crystalline compound with a molecular formula of C4H12ClN5 (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. The structural formula is as shown:

GLUCOVANCE® (Glyburide and Metformin HCl Tablets) Structural Formula Illustration

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.

What side effects may occur?

2008-08-14T08:22:00.001-07:00

Side effects cannot be anticipated. If any develop or change in intensity, inform your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking Glucovance.

* More common side effects may include:
Cold sweats, diarrhea, dizziness, headache, hunger, nausea, shakiness, stomach pain, upper respiratory infections, vomiting

Most important fact about Glucovance

2008-08-14T08:21:00.002-07:00

Very rarely, Glucovance has been known to cause a dangerous condition called lactic acidosis, a buildup of lactic acid in the blood. Lactic acidosis is a medical emergency that requires immediate treatment in the hospital. Notify your doctor without delay if you experience any of the following symptoms:

A slow or irregular heartbeat; a cold, dizzy, or light-headed feeling; a weak, tired, or uncomfortable feeling; stomach discomfort; trouble breathing; unusual muscle pain
How should you take Glucovance?

Glucovance is taken once or twice a day with meals.

--If you miss a dose...

Take it as soon as you remember. If it is almost time for your next dose, skip the one you missed and go back to your regular schedule. Never take 2 doses at the same time.

--Storage instructions...

Store at room temperature and protect from light.

Why Glucovance Prescribed?

2008-08-14T08:21:00.001-07:00

Glucovance is used in the treatment of type 2 (noninsulin dependent) diabetes. Diabetes develops when the body's ability to burn sugar declines and the unused sugar builds up in the bloodstream. Ordinarily, sugar is moved out of the blood and into the body's cells by the hormone insulin. A buildup occurs when the body either fails to make enough insulin or doesn't respond to it properly.
Glucovance is a combination of 2 drugs--glyburide (DiaBeta, Micronase) and metformin (Glucophage)--that attack high blood sugar levels in several ways. The glyburide component stimulates the pancreas to produce more insulin and helps the body use it properly. The metformin component also encourages proper insulin utilization, and in addition works to decrease sugar production and absorption.

Glucovance is prescribed when diet and exercise prove insufficient to keep blood sugar levels under control. Glucovance can also be combined with other diabetes drugs such as Avandia.

Your Lipid Profile

2008-08-09T22:55:00.000-07:00

When doctors order a lab test called a lipid profile (sometimes called a lipid panel), they are looking for information about the amounts of four types of fats in the blood. You will be asked to give a small sample of blood from your arm. The results can help your doctor evaluate your risk for heart disease.

* Cholesterol helps the body form hormones, vitamin D and other important substances, but too much of it in the blood can clog and damage the blood vessels. Because it is a fat-like substance that doesn't mix with blood, cholesterol has to combine with proteins to form lipoproteins. Lipoproteins can travel in the blood to all the organs and tissues of the body.
* Low-density lipoproteins (LDLs, or "bad" cholesterol) build up in the blood and increase your risk of heart disease.
* High-density lipoproteins (HDLs, or "good" cholesterol) carry cholesterol to the liver, where it is removed from the body.
* Triglycerides store energy for your body to use when it is needed. If there is too much, it can block blood vessels and cause other health problems such as abdominal pain and pancreatitis.

It's important to know that the ranges listed below are the most common results, and apply mainly to people without existing medical problems. The ideal range for each person depends on individual risk factors, including conditions such as diabetes or heart disease. Your doctor will help you determine the levels that are healthiest for you.

Mg/dl means milligrams per deciliter. This is a way to measure tiny amounts of substances (a milligram is one-thousandth of a gram) in one deciliter (one-tenth of a liter) of your blood.

The symbol < means "less than."
The symbol > means "more than."

Total Cholesterol (lower is better)

Best = <200 mg/dL
Borderline high = 200-239 mg/dL
High = 240 mg/dL or higher

Triglycerides (lower is better)

Best = <150 mg/dL
Borderline high = 150-199 mg/dL
High = 200-499 mg/dL
Very high = 500 mg/dl or higher

LDL Cholesterol (lower is better)

Best = <100 mg/dL
Good = 100-129 mg/dL
Borderline high = 130-159 mg/dL
High = 160-189 mg/dL
Very high = 190 mg/dL or higher

HDL Cholesterol (higher is better)

Low = <40 mg/dL
Best = 60 mg/dL or higher

Risk Factors
Certain conditions or behaviors will increase your risk for heart disease. The major risk factors include:

* Smoking
* High blood pressure or on blood pressure medication
* Low HDL cholesterol
* Family history of early heart disease (heart disease in father or brother before age 55; heart disease in mother or sister before age 65)
* Age (men 45 years or older; women 55 years or older)

Some of these can be changed (like smoking or diet) and some cannot (like age or family history). You can ask your doctor for advice on how to change what you can.

If you already have some risk factors, your doctor might ask you to make changes to your lifestyle - like losing weight and exercising more - and/or recommend medications to lower your cholesterol.

Your doctor will most likely recommend lifestyle changes and consider drug therapy when:

* You are considered high risk because you already have heart disease.
* You are considered at moderately high risk of heart disease because you have 2 or more major risk factors in addition to other health conditions, and you have an LDL of 100 or more.
* You are considered at moderate risk of heart disease because you have two or more major risk factors and your LDL is 160 or more.
(If your LDL is 130 - 159, only lifestyle changes - not drug therapy - might be recommended.)
* You are considered at lower risk of heart disease because you have 0 or 1 risk factors and your LDL is 190 or more.
(If your LDL is 160 - 189, lifestyle changes will be recommended and drug therapy might be considered.)

Lipid Profile

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A blood test, or the results of a blood test, that measures levels of lipids, or fats, including cholesterol and triglycerides. Factors such as your age, sex, and genetics influence your lipid profile. Certain aspects of your lifestyle, including your diet, level of physical activity, level of diabetes control, and smoking status, also affect your lipid profile. And some medical conditions can raise or lower cholesterol and triglyceride levels.

A lipid profile is a direct measure of three blood components: cholesterol, triglycerides, and high-density lipoproteins (HDLs). Cholesterol is a vital substance that your body uses to produce such things as digestion-aiding material, hormones, and cell membranes. It is both produced by the body and absorbed from some of the foods you eat. Cholesterol and triglycerides are transported in the blood by combinations of lipids and proteins called lipoproteins. HDLs, the so-called "good" or "healthy" cholesterol, are lipoproteins made mostly of protein and little cholesterol. HDLs can help to clear cholesterol deposits in blood vessels left by another blood component called low-density lipoproteins, or LDLs.

LDL levels may be calculated from the three directly measured lipids or may be more accurately measured by a direct test. LDLs and very-low-density lipoproteins (VLDLs) are the so-called "bad" cholesterols. Unlike HDLs, LDLs and VLDLs are high-cholesterol particles. While cholesterol is necessary for various bodily functions, too much cholesterol is harmful, since excess cholesterol can be deposited in blood vessel walls. These fat deposits can lead to atherosclerosis, or hardening of the arteries, and cardiovascular disease, the number one killer in the United States. High levels of triglycerides are also associated with an increased risk of heart disease.

People with Type 1 diabetes whose blood glucose levels are controlled tend to have lipid levels similar to people who don't have diabetes and may even have higher levels of HDL, possibly because of the effects of insulin. People who have Type 2 diabetes, however, tend to have high levels of triglycerides and low HDL levels. And while people with Type 2 diabetes tend to have similar LDL levels as people who don't have diabetes, their LDL particles seem to be smaller and more prone to causing damage. Premenopausal women who do not have diabetes tend to have better cholesterol levels than men, but this protective effect seems to be negated in women with diabetes. Both sexes show an increase in lipoprotein levels as they age.

The American Diabetes Association (ADA) recommends that people with diabetes who have lipid levels that need correction have a lipid profile taken at least annually. Because alcohol and food intake before the test can cause temporary elevations of cholesterol and triglycerides, it is necessary to fast for 9-12 hours before the test and to abstain from alcohol for 24 hours before.

According to the ADA, low-risk cholesterol levels in adults with diabetes are LDL levels below 100 mg/dl, HDL levels above 40 mg/dl (above 50 mg/dl for women), and triglycerides below 150 mg/dl. If all your levels fall in these low-risk categories, you and your doctor may decide that you only need to have a lipid profile done every two years. People with diabetes who have cholesterol levels out of the low-risk ranges may be given a repeat test to verify the results.

A child with diabetes older than two years should be tested at the time of diagnosis if there is a family history of high cholesterol or heart disease or if family history is unknown. If there is no family history of high cholesterol or heart disease, the child should be tested at puberty. Children 12 and older who are diagnosed with diabetes should have a lipid profile done at the time of diagnosis and again after blood sugar levels have been brought under control. Subsequent checks of children need only be done every five years if levels are acceptable.

Comparison of Glyburide

2008-08-02T03:22:00.000-07:00

A direct comparison of glyburide and pioglitazone monotherapy among patients with recently diagnosed type 2 diabetes mellitus demonstrated that pioglitazone is a safe and effective first-line treatment for long-term use. The overall tolerability, adverse-effect profile, and improved level of glycemic control with glyburide and pioglitazone in this trial are consistent with those of previous reports that compared sulfonylureas and thiazolidinediones.[14-16]

After 56 weeks of treatment, glycemic control based on A1C was comparable between the glyburide and pioglitazone groups. However, the profile of A1C measurements from 16-56 weeks suggests a trend of deteriorating glycemic control in the glyburide group and sustained glycemic control in the pioglitazone group. Although these trends are subtle, this observation is consistent with that of reports comparing pioglitazone and gliclazide[14,15] as well as reports on sulfonylurea therapy in the United Kingdom Prospective Diabetes Study (UKPDS).[16] Because these trials enrolled only patients with recently diagnosed type 2 diabetes mellitus, one possibility for deteriorating glycemic control with sulfonylurea monotherapy may have been declining β-cell function with disease progression. The A1C profile from the current study suggests that pioglitazone sustains its efficacy over a longer time than do sulfonylureas and indicates possible β-cell-sparing effects with pioglitazone.[17] Consistent with this possibility, early discontinuation of treatment was greater with glyburide than pioglitazone monotherapy, which in part was attributable to lack of therapeutic efficacy.

The frequency of adverse events leading to study drug discontinuation was also higher with glyburide than pioglitazone. Not unexpectedly, hypoglycemia was the most common adverse event leading to glyburide treatment discontinuation. Adverse events typically attributed to thiazolidinedione therapy, such as edema and weight gain, were observed with both treatments during this trial. Although edema affecting the extremities was reported by more patients treated with pioglitazone than with glyburide, each event was classified as mild or moderate, except one case of severe edema in a pioglitazone-treated patient. The weight increase observed with either treatment is also consistent with results reported in other controlled clinical trials and is a known adverse effect of both drugs.[13] Several interrelated factors, including decreased glycosuria and caloric retention with improved glycemic control, expansion of the subcutaneous fat depot, and fluid retention have been suggested explanations for weight gain with thiazolidinediones.[18]

Overall, a greater mean decrease in ALT was noted with pioglitazone than with glyburide. In addition, a higher proportion of patients treated with glyburide exceeded the upper limit of normal for ALT at the final visit compared with patients treated with pioglitazone. Together these findings support previous reports that pioglitazone reduces hepatic fat content and is not associated with hepatotoxic adverse effects.19

Although this study was not powered to evaluate cardiac outcomes, the frequency of cardiac disorders was 2-fold greater in glyburide than pioglitazone treated patients. Of note, congestive heart failure was reported in only two patients in the trial, one in each treatment group. However, patients with New York Heart Association class III or IV cardiac disorders were not included in this trial.

Interpretation of the study results is limited by the high rate of patient withdrawal. However, the rate of attrition likely did not introduce a selection bias, as an equivalent number of subjects in each treatment group (glyburide 49.0%, pioglitazone 46.6%) withdrew from the study before week 56. Another limitation of this study is that patients were not treated with exactly comparable doses of pioglitazone and glyburide. Patients in the pioglitazone group were taking a mean daily dose of approximately 36 mg (maximum recommended dose 45 mg), whereas patients in the glyburide group were taking a mean daily dose of approximately 10 mg (maximum recommended dose 20 mg). However, since this study was designed as a treat-to-target study, investigators were instructed to adjust the study drug dosage as necessary to achieve and maintain a fasting plasma glucose level between 69 and 141 mg/dl. The observation that glycemic control was equivalent between groups indicates that the investigators complied with this objective.

Metformin Hydrochloride

2008-08-02T03:21:00.000-07:00

Lactic acidosis

Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with glyburide and metformin hydrochloride; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (> 5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels > 5 mcg/mL are generally found.

The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient’s age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Glyburide and metformin hydrochloride treatment should not be initiated in patients ≥ 80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, glyburide and metformin hydrochloride should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, glyburide and metformin hydrochloride should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking glyburide and metformin hydrochloride, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, glyburide and metformin hydrochloride should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS).

The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient’s physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). Glyburide and metformin hydrochloride tablets should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose, and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of glyburide and metformin hydrochloride, gastrointestinal symptoms, which are common during initiation of therapy with metformin, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.

Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking glyburide and metformin hydrochloride do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. (See also PRECAUTIONS.)

Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).

Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking glyburide and metformin hydrochloride, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS).

Cholesterol Reducing Drugs

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Cholesterol-reducing drugs are medicines that lower the amount of cholesterol (a fat-like substance) in the blood.

Purpose

Cholesterol is a chemical that can both benefit and harm the body. On the good side, cholesterol plays important roles in the structure of cells and in the production of hormones. But too much cholesterol in the blood can lead to heart and blood vessel disease. To complicate matters, not all cholesterol contributes to heart and blood vessel problems. One type, called high-density lipoprotein (HDL) cholesterol, or "good cholesterol," actually lowers the risk of these problems. The other type, low-density lipoprotein (LDL) cholesterol, or "bad cholesterol," is the type that threatens people's health. The names reflect the way cholesterol moves through the body. To travel through the bloodstream, cholesterol must attach itself to a protein. The combination of a protein and a fatty substance like cholesterol is called a lipoprotein.

Many factors may contribute to the fact that some people have higher cholesterol levels than others. A diet high in certain types of fats is one factor. Medical problems such as poorly controlled diabetes, an underactive thyroid gland, an overactive pituitary gland, liver disease or kidney failure also may cause high cholesterol levels. And some people have inherited disorders that prevent their bodies from properly using and eliminating fats. This allows cholesterol to build up in the blood.

Treatment for high cholesterol levels usually begins with changes in daily habits. By losing weight, stopping smoking, exercising more and reducing the amount of fat and cholesterol in the diet, many people can bring their cholesterol levels down to acceptable levels. However, some may need to use cholesterol-reducing drugs to reduce their risk of health problems.

Description

There are four different classes of cholesterol lowering drugs:

Bile acid sequesterants are drugs that act by binding with the bile produced by the liver. Bile helps the digestion and absorption of fats in the intestine. By blocking the digestion of fats, bile acid sequesterants prevent the formation of cholesterol. Drugs in this class include: cholestyramine (Questran); colestipol (Colestid); and colesevalam (Welchol).

HMG-CoA inhibitors, often called "statins," are drugs that block an enzyme called "3-hydroxy-3-methyl-glutaryl-coenzyme A reductase." This blocks one of the steps in converting fat to cholesterol. These are the most effective cholesterol lowering agents available and in recent years have received increased attention for their benefits beyond helping patients with high cholesterol. In 2003, researchers reported that people with heart failure but no coronary artery disease received benefits after only 14 weeks of statin therapy. In addition, some research has connected the drugs to reduced risk for depression and dementia. Drugs in this group include: atorvastatin (Lipitor); cerivastatin (Baycol); fluvastatin (Lescol); lovastatin (Mevacor); pravastatin (Pravachol); simvastatin (Zocor); and the newest approved drug rosuvastatin (Crestor).

Fibric acid derivatives include clofibrate (Atromid-S); gemfibrozil (Lopid); and fenofibrate (Tricor). Although these drugs are less effective than the statins at lowering total cholesterol, they may be able to lower the low density lipoprotein (LDL) cholesterol while raising the high density lipoprotein (HDL) cholesterol. They probably act by inhibiting lipoprotein lipase activity.

Niacin, or vitamin B-3, also is effective in lowering cholesterol levels. Although the normal vitamin dose of niacin is only 20 mg, the dose required to reduce cholesterol levels is at least 500 mg each day. Niacin probably helps reduce cholesterol by inhibiting very low density lipoprotein (VLDL) secretion in the bloodstream.

Recommended dosage

The recommended dosage depends on the type of cholesterol-reducing drug used. The prescribing physician or the pharmacist who filled the prescription can advise about the correct dosage.

Cholesterol-reducing drugs should be taken exactly as directed and doses should not be missed. Double doses should not be taken to make up for a missed dose.

Physicians may prescribe a combination of cholesterol-reducing drugs, such as pravastatin and colestipol. Following the directions for how and when to take the drugs is very important. The medicine may not work properly if both drugs are taken at the same time of day.

Niacin should not be taken at the same time as an HMG-CoA inhibitor, as this combination may cause severe muscle problems. If niacin is taken in an over-the-counter form, both the prescribing physician and pharmacist should be informed. There are no problems when the niacin is taken in normal doses as a vitamin.

The prescription should not be stopped without first checking with the physician who prescribed it. Cholesterol levels may increase when the medicine is stopped, and the physician may prescribe a special diet to make this less likely.

Precautions

Seeing a physician regularly while taking cholesterol-reducing drugs is important. The physician will check to make sure the medicine is working as it should and will decide whether it is still needed. Blood tests and other medical tests may be ordered to help the physician monitor the drug's effectiveness and check for side effects.

For most people, cholesterol-reducing drugs are just one part of a whole program for lowering cholesterol levels. Other important elements of the program may include weight loss, exercise, special diets, and changes in other habits. The medication should never be viewed as a substitute for other measures ordered by the physician. Cholesterol-reducing drugs will not cure problems that cause high cholesterol; they will only help control cholesterol levels.

People over 60 years of age may be unusually sensitive to the effects of some cholesterol-reducing drugs. This may increase the chance of side effects.

Anyone who is taking an HMG-CoA reductase inhibitor should notify the health care professional in charge before having any surgical or dental procedures or receiving emergency treatment.

Special conditions

People who have certain medical conditions or who are taking certain other medications may have problems if they take cholesterol-reducing drugs. Before taking these drugs, the prescribing physician should be informed of any of the following conditions:

ALLERGIES

Anyone who has had unusual reactions to cholesterol-reducing drugs in the past should inform the prescribing physician before taking the drugs again. The physician also should be told about any allergies to foods, dyes, preservatives, or other substances.

PREGNANCY

Studies of laboratory animals have shown that giving high doses of gemfibrozil during pregnancy increases the risk of birth defects and other problems, including death of the unborn baby. The effects of this drug have not been studied in pregnant women. Women who are pregnant or who may become pregnant should check with their physicians before using gemfibrozil.

Cholesterol-reducing drugs in the group known as HMG-CoA reductase inhibitors (such as lovastatin, fluvastatin, pravastatin and simvastatin) should not be taken by women who are pregnant or who plan to become pregnant soon. By blocking the production of cholesterol, these drugs prevent a fetus from developing properly. Women who are able to bear children should use an effective birth control method while taking these drugs. Any woman who becomes pregnant while taking these drugs should check with her physician immediately.

Cholestyramine and colestipol will not directly harm an unborn baby, because these drugs are not taken into the body. However, the drugs may keep the mother's body from absorbing vitamins that she and the baby need. Pregnant women who take these drugs should ask their physicians whether they need to take extra vitamins.

BREASTFEEDING

Because cholestyramine and colestipol interfere with the absorption of vitamins, women who use these drugs while breastfeeding should ask their physicians if they need to take extra vitamins.

Women who are breastfeeding should talk to their physicians before using gemfibrozil. Whether this drug passes into breast milk is not known. But because animal studies suggest that it may increase the risk of some types of cancer, women should carefully consider the safety of using it while breastfeeding.

HMG-CoA reductase inhibitors (such as lovastatin, pravastatin, fluvastatin and simvastatin) should not be used by women who are breastfeeding their babies.

OTHER MEDICAL CONDITIONS

Cholesterol-reducing drugs may make some medical problems worse. Before using these drugs, people with any of these medical conditions should make sure their physicians are aware of their conditions:

* stomach problems, including stomach ulcer

* constipation

* hemorrhoids

* gallstones or gallbladder disease

* bleeding problems

* underactive thyroid

* heart or blood vessel disease

In addition, people with kidney or liver disease may be more likely to have blood problems or other side effects when they take certain cholesterol-reducing drugs. And some drugs of this type may actually raise cholesterol levels in people with liver disease.

Patients with any of the following medical conditions may develop problems that could lead to kidney failure if they take HMG-CoA reductase inhibitors:

* treatments to prevent rejection after an organ transplant

* recent major surgery

* seizures (convulsions) that are not well controlled

People with phenylketonuria (PKU) should be aware that sugar-free formulations of some cholesterol-reducing drugs contain phenylalanine in aspartame. This ingredient can cause problems in people who have phenylketonuria.

USE OF CERTAIN MEDICINES

Cholesterol-reducing drugs may change the effects of other medicines. Patients should not take any other medicine that has not been prescribed or approved by a physician who knows they are taking cholesterol-reducing drugs.

Side effects

Gemfibrozil

Studies in animals and humans suggest that gemfibrozil increases the risk of some types of cancer. The drug may also cause gallstones or muscle problems. Patients who need to take this medicine should ask their physicians for the latest information on its benefits and risks.

Patients taking gemfibrozil should check with a physician immediately if any of these side effects occur:

* fever or chills

* severe stomach pain with nausea and vomiting

* pain in the lower back or side

* pain or difficulty when urinating

* cough or hoarseness

HMG-CoA reductase inhibitors

These drugs may damage the liver or muscles. Patients who take the drugs should have blood tests to check for liver damage as often as their physician recommends. Any unexplained pain, tenderness or weakness in the muscles should be reported to the physician at once.

All cholesterol-reducing drugs

Minor side effects such as heartburn, indigestion, belching, bloating, gas, nausea or vomiting, stomach pain, dizziness and headache usually go away as the body adjusts to the drug and do not require medical treatment unless they continue or they interfere with normal activities.

Patients who have constipation while taking cholesterol-reducing drugs should bring the problem to a physician's attention as soon as possible.

Additional side effects are possible. Anyone who has unusual symptoms while taking cholesterol-reducing drugs should get in touch with his or her physician.

Interactions

Cholesterol-reducing drugs may interact with other medicines. When this happens, the effects of one or both of the drugs may change or the risk of side effects may be greater. Anyone who takes cholesterol-reducing drugs should let the physician know all other medicines he or she is taking and should ask whether the possible interactions can interfere with drug therapy. Examples of possible interactions are listed below.

Some cholesterol-reducing drugs may prevent the following medicines from working properly:

* thyroid hormones

* water pills (diuretics)

* certain antibiotics taken by mouth, such as tetracyclines, penicillin G and vancomycin

* the beta-blocker Inderal, used to treat high blood pressure

* digitalis heart medicines

* phenylbutazone, a nonsteroidal anti-inflammatory drug

Taking some cholesterol-reducing drugs with blood thinners (anticoagulants) may increase the chance of bleeding.

Combining HMG-CoA reductase inhibitors with gemfibrozil, cyclosporine (Sandimmune) or niacin may cause or worsen problems with the kidneys or muscles.

Key Terms

Cell
The basic unit that makes up all living tissue.

Cholesterol
Fatty substance found in tissue. Necessary to maintain a healthy body.

Enzyme
A type of protein, produced in the body, that brings about or speeds up chemical reactions.

Hormone
A substance that is produced in one part of the body, then travels through the bloodstream to another part of the body where it has its effect.

Phenylketonuria
(PKU) A genetic disorder in which the body lacks an important enzyme. If untreated, the disorder can lead to brain damage and mental retardation.

Pituitary gland
A pea-sized gland at the base of the brain that produces many hormones that affect growth and body functions.

Taste of Future?

2008-07-28T05:52:00.000-07:00

"Ice cream is the nectar of the gods. This is a fat-free nectar." According to USA Today, that's what its reporter Pat Guy had to say about the new frozen dessert Simple Pleasures.

Mark Memmott of the same paper was less enthusiastic. "The chocolate leaves a rather unpleasant aftertaste," he said. "I wouldn't serve it to my dog. I'd give it to the cat. I don't like the cat." Editor Ray Goldbacher's verdict was more middle-of-the-road: "I don't think anyone will mistake this for super-premium ice cream, but it's not bad."

Pronouncements on the taste of this new dessert varied similarly among others present at the press conference held in February 1990 to introduce the product to the public.

What's all the fuss about? It's about ice cream without fat. Ice cream without guilt. (Well, maybe some guilt even though it's fat-free, it's not calorie-free.)

Simple Pleasures is a frozen dessert made with Simplesse, the first fat substitute approved by the Food and Drug Administration. In fact, legally, Simple Pleasures cannot be called ice cream because FDA's standards of identity require that ice cream contain at least 10 percent butterfat. Both Simple Pleasures and Simplesse are products of NutraSweet Co., a subsidiary of Monsanto Co. of St. Louis, Mo. (NutraSweet also makes aspartame, the sugar substitute widely used in low-calorie beverages and other products.)

Simplesse is promoted as a competitor for premium ice creams. In petitioning FDA for approval of Simplesse, NutraSweet compared the fat, cholesterol and caloric content of a super-premium vanilla ice cream containing 16 percent butterfat with a frozen dessert using Simplesse. A 4-ounce serving of the ice cream provided 19 grams of fat, 97 milligrams of cholesterol, and 274 calories, whereas the same size serving of Simple Pleasures contained less than 1 gram of fat, 14 milligrams of cholesterol, and 120 calories. Regular ice cream, with approximately 10 percent fat, contains about 7 grams of fat, 30 milligrams of cholesterol, and 135 calories per 4-ounce serving. (Simple Pleasures is not yet available in vanilla because, the company says, it hasn't yet been able to get the taste just right. It now offers toffee crunch, chocolate, strawberry, coffee, peach, and rum raisin.)
Simplesse is made from egg white and milk protein blended and heated in a process called microparticulation, in which the protein is shaped into microscopic round particles that roll easily over one another. The aim of the process is to create the feel of a creamy liquid with the texture of fat.

It works. Because its components have long been used as foods, FDA, on Feb. 23,1990, affirmed Simplesse as "generally recognized as safe" (GRAS) for use as a thickener or texturizer in frozen dessert products. Safety studies were not required.

NutraSweet plans to seek FDA approval for use of Simplesse in additional products, such as mayonnaise, salad dressing, yogurt, dips, sour cream, butter, margarine, and cheese spreads. Simplesse cannot be used in cooking because baking or frying causes it to lose its creaminess. NutraSweet says, however, that "products made with Simplesse can be enjoyed with many hot foods." For example, it can be used in an imitation butter spread on toast or in a sour cream-type sauce used to top a baked potato.

NutraSweet estimates that full use of Simplesse has the potential to decrease total dietary fat consumption by Americans by 14 percent and dietary cholesterol intake by 5 percent.

Other fat substitutes are under development or awaiting FDA approval. Kraft General Foods has petitioned the agency for GRAS approval of Trailblazer, which, like Simplesse, is made from egg and milk protein processed to mimic the "mouth feel" of fat.

Procter and Gamble's fat substitute Olestra, however, is a different matter. Developed for use in hot foods as well as cold, it is a new substance that, according to the company, is "almost a carbon copy of regular fat, but with a molecule of sugar at its core instead of glycerine, and up to eight fatty acids attached to the core instead of the customary three."

Because it is a new molecular structure that does not break down to its component parts during digestion, Olestra must be approved as a new food additive rather than as a GRAS substance, which means that studies must be done to ensure its safety.

Procter and Gamble says its product looks, tastes, feels, and behaves like fat. It cooks without breaking down under heat, yet it cannot be digested and absorbed, so it passes through the body "contributing no calories, no cholesterol, and no fat." The company is asking for approval of Olestra for deep-frying savory snacks such as chips and puffs made from potatoes and corn.

Health- and weight-conscious consumers are expected to welcome fat-free products that taste like the real thing. In fact, a recent survey by the Calorie Control Council, an association of low-calorie and diet food manufacturers, found that 57 percent of adult Americans believe there is a need for fat substitutes.

According to the 1988 Surgeon General's Report on Nutrition and Health, high intake of fat is associated with increased risk for obesity, some types of cancer (breast, colon, prostate, rectum, ovaries, and endometrium), and possibly gallbladder disease. Studies also show strong evidence of a relationship between high saturated fat intake and a high blood cholesterol level, which is a risk factor for coronary heart disease.

The report also states that because obesity is a risk factor for several chronic diseases, it is important to maintain a desirable weight. Obesity increases the risk of high blood pressure and, consequently, stroke. It also increases blood cholesterol and may, by itself, be a risk factor for coronary heart disease.

Because fat contributes nine calories per gram, fat substitution would significantly reduce the calorie content of a food. Excess calories from fat are readily stored and cause weight gain.

A 1985 national survey by the U.S. Department of Agriculture found that fat contributed 34 percent of total calorie intake for children ages 1 to 5, 36 percent for men ages 19 to 50, and 37 percent for women ages 19 to 50. The National Cholesterol Education Program of the National Heart, Lung, and Blood Institute, along with other health groups, recommends that all healthy Americans 2 and older limit their total daily fat intake to no more than 30 percent of total calories and that less than 10 percent of the total calories should be from saturated fat. Cholesterol should be kept to less than 300 milligrams per day, and the total calorie intake should be what is needed to reach or maintain a desirable weight. (People with certain illnesses or conditions may have different requirements.)

It remains to be seen, however, whether consumers will, indeed, become healthier by using products with fat substitutes. According to the June 15,1990, issue of The Medical Letter, a professional publication on drugs and therapeutics, no clinical studies have shown that use of either Simplesse or Trailblazer leads to weight reduction or decreases blood lipid (fat) concentrations.

Moreover, some nutritionists are concerned that people who eat products made with fat substitutes will feel freer to eat more of other high-fat foods, rationalizing that they are "saving" on those made with substitutes. Another possibility experts anticipate is that people will eat more fat-free double-dip ice cream cones, leaving less room for the more nutritious foods they need.

A more basic, as yet unanswered, question is whether nonfat foods will satisfy as well as the traditional foods they replace and, therefore, whether they will really help people reduce fat consumption.

Lisa Lefferts, staff scientist with the Washington-based consumer advocacy group Center for Science in the Public Interest, points to the experience with sugar substitutes: "We're eating four times the amount of sugar substitutes as we were in 1975, but sugar consumption has gone up as well, so clearly sugar substitutes are not substituting for sugar." Lefferts says that the effect of fat substitutes on the diet is unclear. "Fat substitutes such as Simplesse are a step in the right direction," she says, "but we would encourage that their use be monitored in order to assess their true impact."

FDA, too, has questions about the impact of fat substitutes in the food supply. "There are two categories of fat substitutes to consider," says Walter Glinsmann, M.D., associate director for clinical nutrition. "Products like Simplesse are processed from substances already in the diet, and they are digested and used by the body in the same way as the original substances. Others, like Olestra, are new, undigestible molecules never before in the food supply."

The possible health effects of consuming large amounts of a novel substance must be carefully researched and reviewed before such a product can be marketed. "When you consider that fat intake is about 35 to 40 percent of the daily caloric intake and that half of that fat is derived from foods in which the fat can be replaced with a substitute, you need to take a hard look at the potential health effects," Glinsmann cautions.

Some of the questions to be considered are:

* If the materials are absorbed in the body even in very small amounts are they toxic?
* If they are not absorbed, how do they affect gastrointestinal functions? For example, could they interfere with the absorption of nutrients or drugs?
* Are the substitutes suitable for general use or only for subpopulations of the general public?

The financial impact of fat substitutes may be easier to predict than the health and dietary effects. In February 1990, The Wall Street Journal reported that some estimates have Simplesse becoming a $500-million-a-year or bigger business by the mid-199Os. It is not surprising that still more firms, in addition to Kraft and Procter and Gamble, are entering the race for these consumer dollars.

Type 2 Diabetes

2008-07-25T04:00:00.001-07:00

Definition

Type 2 diabetes is a life-long disease marked by high levels of sugar in the blood. It occurs when the body does not respond correctly to insulin, a hormone released by the pancreas. Type 2 diabetes is the most common form of diabetes.

See also:

* Diabetes
* Type 1 diabetes
* Gestational diabetes

Alternative Names

Noninsulin-dependent diabetes; Diabetes - type 2
Causes, incidence, and risk factors

Diabetes is caused by a problem in the way your body makes or uses insulin. Insulin is needed to move glucose (blood sugar) into cells, where it is used for energy.

If glucose does not get into the cells, the body cannot use it for energy. Too much glucose will then remain in the blood, causing the symptoms of diabetes.

There are several types of diabetes. This article focuses on type 2, which is usually accompanied by obesity and insulin resistance.

Insulin resistance means that insulin produced by your pancreas cannot get inside fat and muscle cells to produce energy. Since the cells are not getting the insulin they need, the pancreas produces more and more. Over time, abnormally high levels of sugar build up in the blood. This is called hyperglycemia. Many people with insulin resistance have hyperglycemia and high blood insulin levels at the same time. People who are overweight have a higher risk of insulin resistance, because fat interferes with the body's ability to use insulin.

Type 2 diabetes usually occurs gradually. Most people with the disease are overweight at the time of diagnosis. However, type 2 diabetes can also develop in those who are thin, especially the elderly.

Family history and genetics play a large role in type 2 diabetes. Low activity level, poor diet, and excess body weight (especially around the waist) significantly increase your risk for type 2 diabetes.

Other risk factors include:

* Race/ethnicity (African-Americans, Hispanic-Americans, and Native Americans all have high rates of diabetes)
* Age greater than 45 years
* Previously identified impaired glucose tolerance by your doctor
* High blood pressure
* HDL cholesterol of less than 35 mg/dL or triglyceride level of greater than 250 mg/dL
* History of gestational diabetes

Symptoms

Often, people with type 2 diabetes have no symptoms at all. If you do have symptoms, they may include:

* Increased thirst
* Increased urination
* Increased appetite
* Fatigue
* Blurred vision
* Frequent or slow-healing infections
* Erectile dysfunction

Signs and tests

Type 2 diabetes is diagnosed with the following blood tests:

* Fasting blood glucose level -- diabetes is diagnosed if higher than 126 mg/dL on 2 occasions.
* Random (non-fasting) blood glucose level -- diabetes is suspected if higher than 200 mg/dL and accompanied by the classic symptoms of increased thirst, urination, and fatigue (this test must be confirmed with a fasting blood glucose test).
* Oral glucose tolerance test -- diabetes is diagnosed if glucose level is higher than 200 mg/dL after 2 hours.

Treatment

The first goals are to eliminate the symptoms and stabilize your blood glucose levels. The ongoing goals are to prevent long-term complications and prolong your life. The primary treatment for type 2 diabetes is exercise and diet.

LEARN THESE SKILLS

You should learn basic diabetes management skills. They will help prevent complications and the need for medical care. These skills include:

* How to test and record your blood glucose (see blood glucose monitoring)
* What to eat and when
* How to take medications, if indicated
* How to recognize and treat low and high blood sugar
* How to handle sick days
* Where to buy diabetes supplies and how to store them

It may take several months to learn the basic skills. Always continue to educate yourself about the disease and its complications, as well as how to control and live with diabetes. Over time, stay current on new research and treatment.

SELF-TESTING

Regular self-testing of your blood sugar tells you how well your combination of diet, exercise, and medication are working. Tests are usually done before meals and at bedtime. More frequent testing may be needed when you are sick or under stress.

A device called a glucometer can provide an exact blood sugar reading. There are different types of devices. Usually, you prick your finger with a small needle called a lancet, which gives you a tiny drop of blood. You place the blood on a test strip, and put the strip into the device. Results are available within 30 to 45 seconds.

A health care provider or diabetes educator will help set up an appropriate testing schedule for you. You will also be taught how to respond to different ranges of glucose values obtained when you self-test.

The results of the test can be used to adjust meals, activity, or medications to keep blood sugar levels in an appropriate range. Testing provides valuable information for the health care provider and identifies high and low blood sugar levels before serious problems develop.

Accurate record keeping of test results will help you and your health care provide plan how to best control your diabetes.

DIET AND WEIGHT CONTROL

Meal planning includes choosing healthy foods, eating the right amount of food, and eating meals at the right time. You should work closely with your health care provider to learn how much fat, protein, and carbohydrates you need in your diet. Your specific meal plans need to be tailored to your food habits and preferences.

Managing your weight and eating a well-balanced diet are important. Some people with type 2 diabetes can stop medications after intentional weight loss, although the diabetes is still present. A registered dietitian can be helpful in determining your specific, individual dietary needs. (See diabetes diet.)

REGULAR PHYSICAL ACTIVITY

Regular exercise is important for everyone, but especially if you have diabetes. Regular exercise helps control the amount of glucose in the blood. It also helps burn excess calories and fat so you can manage your weight.

Exercise improves overall health by improving blood flow and blood pressure. It decreases insulin resistance even without weight loss. Exercise also increases the body's energy level, lowers tension, and improves your ability to handle stress.

The following should be considered when starting an exercise routine:

* Check with your health care provider before starting an exercise program.
* Choose an enjoyable physical activity that is appropriate for the current fitness level.
* Exercise every day, and at the same time of day, if possible.
* Monitor blood glucose levels at home before and after exercise.
* Carry food that contains a fast-acting carbohydrate in case blood glucose levels get too low during or after exercise.
* Wear a diabetes identification bracelet and carry change or a cell phone for a phone call in case of emergency.
* Drink extra fluids that do not contain sugar before, during, and after exercise.
* Changes in exercise intensity or duration may require modification of your diet or medication to keep blood glucose levels in an appropriate range.

MEDICATION

When diet and exercise do not help maintain normal or near-normal blood glucose levels, your doctor may prescribe medication. Some of the most common types are listed below. They are taken by mouth.

* Oral sulfonylureas (like glimepiride, glyburide, and tolazamide) trigger the pancreas to make more insulin.
* Biguanides (Metformin) tell the liver to decrease its production of glucose, which increases glucose levels in the blood stream.
* Alpha-glucosidase inhibitors (such as acarbose) decrease the absorption of carbohydrates from the digestive tract, thereby lowering the after-meal glucose levels.
* Thiazolidinediones (such as rosiglitazone) help insulin work better at the cell site. In essence, they increase the cell's sensitivity (responsiveness) to insulin. Rosiglitazone may increase the risk of heart problems. Talk to your doctor.
* Meglitinides (including repaglinide and nateglinide) trigger the pancreas to make more insulin in response to how much glucose is in the blood.

If you continue to have poor blood glucose control despite lifestyle changes and taking medicines by mouth, your doctor will prescribe insulin. Insulin may also be prescribed if you have had a bad reaction to other medicines. Insulin must be injected under the skin using a syringe and cannot be taken by mouth.

Insulin preparations differ in how fast they start to work and how long they work. Your healthcare provider will determine the appropriate type of insulin to use and will tell you what time of day to use it.

More than one type may be mixed together in an injection to achieve the best control of blood glucose. Usually injections are needed one to four times a day. Your doctor or diabetes educator will show you how to give yourself an injection.

FOOT CARE

People with diabetes are prone to foot problems. Diabetes can cause damage to nerves, which means you may not feel an injury to the foot until a large sore or infection develops. Diabetes can also damage blood vessels, which makes it harder for the body to fight infection.

To prevent injury to the feet, a person with diabetes should adopt a daily routine of checking and caring for the feet as follows:

* Check your feet every day, and report sores or changes and signs of infection.
* Wash feet every day with lukewarm water and mild soap, and dry them thoroughly.
* Soften dry skin with lotion or petroleum jelly.
* Protect feet with comfortable, well-fitting shoes.
* Exercise daily to promote good circulation.
* See a podiatrist for foot problems, or to have corns or calluses removed.
* Remove shoes and socks during a visit to the health care provider to remind them to examine your feet.
* Stop smoking because it worsens blood flow to the feet.

CONTINUING CARE

A person with type 2 diabetes should have a visit with a diabetes care provider every 3 months. A complete examination includes:

* Glycosylated hemoglobin (HbA1c) is a 3-month average of your blood glucose level. This test measures how much glucose has been sticking to red blood cells and other cells. A high HbA1c is an indicator of risk for long-term complications. Currently, the ADA recommends an HbA1c of less than 7% to protect oneself from complications.
* Blood pressure check
* Foot and skin examination
* Ophthalmoscopy examination
* Neurological examination

The following evaluations should be done at least once a year:

* Random microalbumin (urine test for protein)
* BUN and serum creatinine
* Serum cholesterol, HDL, and triglycerides
* ECG
* Dilated retinal exam

Support Groups

For additional information, see diabetes resources.
Expectations (prognosis)

The risk of long-term complications from diabetes can be reduced. If you control your blood glucose and blood pressure, you can reduce your risk of death, stroke, heart failure, and other complications. Reduction of HbA1c by even 1% can decrease your risk for complications by 25%.
Complications

Emergency complications include diabetic coma.

Long-term complications include:

* Diabetic retinopathy (eye disease)
* Diabetic nephropathy (kidney disease)
* Diabetic neuropathy (nerve damage)
* Peripheral vascular disease (damage to blood vessels/circulation)
* High cholesterol, high blood pressure, atherosclerosis, and coronary artery disease

Calling your health care provider

Call your health care provider immediately if you have:

* Trembling
* Weakness
* Drowsiness
* Headache
* Confusion
* Dizziness
* Double vision
* Lack of coordination

These symptoms can rapidly progress to emergency conditions (such as convulsions, unconsciousness, or hypoglycemic coma).
Prevention

Everyone over 45 should have blood glucose checked at least every 3 years. Regular testing of random blood glucose should begin at a younger age and be performed more often if you are at particular risk for diabetes.

Maintain a healthy body weight and keep an active lifestyle to help prevent the onset of type 2 diabetes.

Pregnancy Implications

2008-07-25T03:57:00.000-07:00

Glyburide was not found to significantly cross the placenta in vitro and was not found in the cord serum infants of mothers taking glyburide for gestational diabetes mellitus (GDM). Reported teratogenic effects may be due to poorly controlled maternal diabetes; abnormal blood glucose levels in the mother are associated with a higher incidence of congenital abnormalities. Nonteratogenic effects such as hypoglycemia in the neonate have been associated with maternal glyburide use. The manufacturer recommends that if glyburide is used during pregnancy, it should be discontinued at least 2 weeks before the expected delivery date. Although studies have shown positive outcomes using glyburide for the treatment of GDM, use may not be appropriate for all women. When compared to insulin for the treatment of GDM, as the severity of GDM increased, the success rate of treatment decreased. It should be noted that studies using glyburide for the treatment of GDM have initiated treatment after the period of organogenesis. Insulin is considered the drug of choice for the control of diabetes mellitus during pregnancy.Reproduction studies differ by manufacturer labeling. Because adverse events were not observed in animal reproduction studies, one manufacturer classifies glyburide as pregnancy category B. Because adverse events were noted in animal studies during the period of lactation, another manufacturer classifies glyburide as pregnancy category C.

Some Other drugs may affect Glyburide

2008-07-18T07:19:00.000-07:00

Many other medicines may increase or decrease the effects of glyburide or affect your condition. Before taking glyburide, tell your doctor if you are taking any of the following medicines:

* aspirin or another salicylate such as magnesium/choline salicylate (Trilisate), salsalate (Disalcid, others), choline salicylate (Arthropan), magnesium salicylate (Magan), or bismuth subsalicylate (Pepto-Bismol);
* a nonsteroidal anti-inflammatory drug (NSAID) such as ibuprofen (Motrin, Advil, Nuprin, others), ketoprofen (Orudis, Orudis KT, Oruvail), diclofenac (Voltaren, Cataflam), etodolac (Lodine), indomethacin (Indocin), nabumetone (Relafen), oxaprozin (Daypro), naproxen (Anaprox, Naprosyn, Aleve), and others;
* a sulfa-based drug such as sulfamethoxazole-trimethoprim (Bactrim, Septra), sulfisoxazole (Gantrisin), or sulfasalazine (Azulfidine);
* a monoamine oxidase inhibitor (MAOI) such as isocarboxazid (Marplan), tranylcypromine (Parnate), or phenelzine (Nardil);
* a beta-blocker such as propranolol (Inderal), atenolol (Tenormin), acebutolol (Sectral), metoprolol (Lopressor), and others;
* a diuretic (water pill) such as hydrochlorothiazide (HCTZ, Hydrodiuril), chlorothiazide (Diuril), and others;
* a steroid medicine such as prednisone (Deltasone, Orasone, others), methylprednisolone (Medrol, others), prednisolone (Prelone, Pediapred, others), and others;
* a phenothiazine such as chlorpromazine (Thorazine), fluphenazine (Prolixin, Permitil), prochlorperazine (Compazine), promethazine (Phenergan), and others;
* phenytoin (Dilantin);
* isoniazid (Nydrazid); or
* prescription, over-the-counter, or herbal cough, cold, allergy, or weight loss medications.

You may require a dosage adjustment or special monitoring if you are taking any of the medicines listed above.

Drugs other than those listed here may also interact with glyburide or affect your condition. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including vitamins, minerals, and herbal products.

Long Term Safety of Glyburide for Diabetes Mellitus

2008-07-18T07:12:00.000-07:00

Pioglitazone is an oral antidiabetic agent of the thiazolidinedione class indicated for use in patients with type 2 diabetes mellitus as an adjunct to diet and exercise or in combination with a sulfonylurea, metformin, or insulin when diet and exercise alone do not result in adequate glycemic control. Thiazolidinediones act on peroxisome proliferator-activated receptors (PPARs), which regulate glucose, lipid, and protein metabolism and influence cell proliferation, differentiation, and apoptosis. Through selective agonism of PPAR-g receptors, thiazolidinediones inhibit hepatic glucogenesis and increase insulin sensitivity in muscle and adipose tissue, lowering glucose levels.3 Because thiazolidinediones do not stimulate insulin secretion but enhance the effects of circulating insulin, the antihyperglycemic effect can be achieved only in the presence of insulin.

In addition to glycemic control, selected thiazolidinediones have been shown to have a beneficial effect on lipid profiles. In support of these findings, several randomized controlled trials have demonstrated improved glycemic control and favorable lipid-altering effects with once-daily pioglitazone or with a combination of pioglitazone plus metformin, a sulfonylurea, repaglinide, or insulin.[4-9] In addition, a recent head-to-head comparison trial of the thiazolidinediones pioglitazone and rosiglitazone demonstrated comparable effects on glycemic control, although pioglitazone significantly lowered triglyceride levels, increased high-density lipoprotein cholesterol levels, and decreased the number of small, dense low-density lipoprotein cholesterol particles compared with rosiglitazone.

Although thiazolidinediones have been associated with weight gain, edema, and slight reductions in hemoglobin and hematocrit levels (as a result of plasma volume expansion), several reports indicate that these adverse events are generally mild to moderate and infrequently lead to discontinuation of pioglitazone or rosiglitazone. Neither pioglitazone nor rosiglitazone has been associated with hepatotoxicity, which is linked to the thiazolidinedione troglitazone.

Oral drugs of the sulfonylurea class, such as glyburide, stimulate insulin secretion by binding to and blocking adenosine 5¢-triphosphate- dependent potassium channels in β-cell membranes. This action increases intracellular calcium concentrations, inducing insulin secretion. Because the therapeutic effect of sulfonylureas depends on their insulin secretory action, development of hypoglycemia is associated with their use.

Type 2 diabetes mellitus is a lifelong disorder requiring long-term treatment. Because, to our knowledge, no long-term safety and efficacy data comparing glyburide with pioglitazone have been collected yet, this study was conducted to determine whether long-term treatment with glyburide versus pioglitazone is safe and effective in achieving and maintaining glycemic control in patients with recently diagnosed type 2 diabetes mellitus inadequately controlled with diet and exercise.

Stop taking glyburide and seek emergency medical attention if you experience an allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives).

Other, less serious side effects from glyburide result mostly from blood sugar levels that are either too high or too low. You should be familiar with the symptoms of both high and low blood sugar levels and know how to treat both conditions. Also, be sure your family and close friends know how to help you in an emergency situation.

Low blood sugar may occur when too much glyburide is taken; when meals are missed or delayed; if you exercise more than usual; during illness, especially with vomiting or diarrhea; if you take other medications; after drinking alcohol; and in other situations.

Hypoglycemia or Low blood sugar has the following symptoms:

* shaking;
* headache;
* cold sweats;
* pale, cool skin;
* anxiety; and
* difficulty concentrating.

Keep hard, sugary candy; chocolate; fruit juice; or glucose tablets on hand to treat episodes of low blood sugar.

Increased blood sugar may occur when not enough glyburide is taken; if you eat significantly more food than usual; if you exercise less than usual; if you take other medications; during fever or other illness; and in other situations.

Hyperglycemia or High blood sugar has the following symptoms:

* increased thirst,
* increased hunger, and
* increased urination.

There may be an increased risk of death due to cardiovascular (heart and blood vessels) complications with the use of glyburide when compared to the treatment of diabetes with diet or diet plus insulin. The long-term use of glyburide should be discussed with your doctor.

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.

Type2 Diabetes

2008-07-09T03:17:00.001-07:00

Description
An in-depth report on the causes, diagnosis, treatment, and prevention of type 2 diabetes.
Alternative Names
Maturity Onset Diabetes; Noninsulin-dependent Diabetes Mellitus
Medications

The American Heart Association now recommends that patients should aim for the following test results for intensive control of glucose levels:

* Fasting plasma glucose concentrations below 110 mg/dL.
* Glycolated hemoglobin (HbA1c) levels of less than 7%. Controlling HbA1c is the most important factor for reducing the risk of complications in patients with diabetes. According to one 2000 study, a 1% reduction in people with elevated glycolated hemoglobin levels lowers the risk for complications by 21%.

Evidence clearly supports strict glycemic control for reducing complications in the nervous system and blood vessels that occur in both type 1 and type 2 diabetes. Although to date tight control of blood glucose has not proven to reduce mortality rates from all causes or cardiovascular diseases in patients with type 2 diabetes, evidence is increasing that intensive control has benefits for the heart as well--although they may not be evident as rapidly.

It is may be difficult for patients with type 2 diabetes to control their blood sugar levels--particularly if they are overweight. On the positive side, metformin (Glucophage), an oral anti-hypoglycemic agent, has many benefits--it helps control blood glucose levels, does not produce weight gain, and also has heart benefits. In comparison with other diabetic agents, including insulin, it is the only proven drug to improve survival rates. A number of oral agents are also available that are beneficial, alone or in combinations. Insulin therapy is often eventually required as natural insulin reserves become depleted.

Managing risk factors for heart disease and stroke, particularly strict control of blood pressure, may more important for improving survival than strict control of blood glucose levels in these patients. Such goals also seem to be more attainable for many patients with type 2 diabetics.

Oral Anti-hyperglycemic Agents (OHAs). Many oral anti-hyperglycemic agents (OHAs) are now available to help patients with for type 2 diabetes control their blood sugar levels. Most of these agents are aimed at using or increasing sensitivity to the patient's own natural stores of insulin. Metformin is the only agent to date that achieves lower mortality rates:

* Biguanides (metformin). Increase tissue sensitivity to available insulin. Metformin also has beneficial effects on cholesterol, blood pressure, and clotting factors. It does not cause weight gain or hypoglycemia. Metformin produces lower mortality rates than other drugs, including insulin, and should be considered as first-line therapy for most type 2 patients who are insulin resistant.
* Sulfonylureas (examples include glyburide, glipizide, and glimepiride). Stimulate insulin secretion.
* Meglitinides (repaglinide, nateglinide). Stimulate insulin secretion. These newer agents are better than sulfonylureas in controlling glucose spikes after meals.
* Thiazolidinediones (pioglitazone and rosiglitazone). Reduce insulin resistance. These agents improve cholesterol levels and may reduce the risk for blood clots. However, they can cause swelling from fluid build-up, which can worsen heart failure or even possibly precipitate it. They also may injure the liver. The drugs have not been intensively studied, and some experts believe they should not be used except in clinical studies.
* Alpha-glucosidase inhibitors (acarbose and miglitol). Slow intestinal absorption of carbohydrates. Have only modest effects and have gastrointestinal side effects.

Combinations of these agents, particularly with metformin, are often used to increase effectiveness. For example, combinations of rosiglitazone and metformin (Avandamet) and glyburide and metformin (Glucovance) are proving to be very effective. Glucovance may be particularly beneficial for patients with unhealthy cholesterol levels and poor control of their blood sugar levels. Some experts recommend the combination as first-line treatment.

Adding Insulin Replacement. Insulin replacement is usually required as natural insulin reserves are depleted. It is typically started it combination with an oral agent. Eventually, some people may need to go on full insulin replacement.
Metformin (a Biguanide)

Metformin (Glucophage) is a biguanide, which appears to work by reducing glucose production in the liver and by making tissues more sensitive to insulin. It is now be considered by many experts to be the first choice for most type 2 patients who are insulin resistant, particularly if they are overweight. Metformin achieves lower mortality rates from diabetes and all causes than other drugs. In one comparison study, it achieved the lowest mortality rates (8%) compared to insulin (28%), a sulfonylurea (16%), and a thiazolidinedione (14%). Combinations with insulin-secreting drugs, other insulin-sensitizing drugs, or insulin itself are particularly effective.

Metformin does not cause hypoglycemia or add weight, so it is particularly well suited for obese type 2 patients. (In some studies, in fact, patients lost weight.) Metformin also appears to have beneficial effects on cholesterol and lipid levels and may be heart protective. Some research, in fact, has suggested that it significantly reduces the risk for heart attack. It is also the first choice for children who need oral agents and is proving to be very effective for women with polycystic ovaries and insulin resistance.

Side Effects. Side effects include the following:

* A metallic taste.
* Gastrointestinal problems, including nausea, and diarrhea.
* It may also reduce absorption of vitamin B12 and folic acid, which are important for protection against heart disease.
* There have been some reports of lactic acidosis, a potentially life-threatening condition, particularly in people with risk factors for it. Major studies, however, found no greater risk with metformin than with any of the other drugs used for type 2 diabetes.

Certain people should not use this drug, including anyone with congestive heart failure or kidney or liver disease. It is rarely suitable for adults over 80.
Sulfonylureas

Sulfonylureas are oral drugs that stimulate the pancreas to release insulin. They are also first-line oral agents. For adequate control of blood glucose levels, the drugs should only be taken 20 to 30 minutes before a meal. A number of brands are available, including chlorpropamide (Diabinese), tolazamide (Tolinase), acetohexamide (Dymelor), glipizide (Glucotrol), tolbutamide (Orinase), glimepiride (Amaryl), glyburide or glibenclamide outside the US (DiaBeta, Micronase), and gliclazide.

Most patients can take sulfonylureas for seven to 10 years before they lose effectiveness. Combinations with small amounts of insulin or with other drugs (such as metformin or a thiazolidinedione) may extend their benefits. In fact, a combination of glyburide and metformin in one pill (Glucovance) is now available. Glucovance may be particularly beneficial for patients with unhealthy cholesterol levels and poor control of their blood sugar levels. Some experts recommend the combination as first-line treatment.

Also encouraging was a 2000 study of patients with severe type 2 diabetes reporting that combinations of insulin with either chlorpropamide or glipizide (two different sulfonylureas) achieved better glucose control over the long term than insulin alone.

Side Effects and Complications. In general, sulfonylureas should not be used by women who are pregnant or nursing or by individuals who are allergic to sulfa drugs. Side effects include the following:

* Weight gain. Some sulfonylureas, such as glimepiride, may produce less weight gain than others.
* Water retention.
* Although sulfonylureas pose a lower risk for hypoglycemia than insulin does, the hypoglycemia produced by sulfonylureas may be prolonged and dangerous. The newer sulfonylureas, such as glimipiride, appear to have about one tenth the risk of hypoglycemia than do older sulfonylureas.
* Some may pose a slight risk for cardiac events.

Sulfonylureas interact with many other drugs, and patients should be sure to inform their physician of any medications they are taking, including alternative or over-the-counter drugs.
Meglitinides

Meglitinides stimulate beta cells to produce insulin. They include repaglinide (Prandin), nateglinide (Starlix), and mitiglinide. These agents are rapidly metabolized and short acting and if taken before every meal, they actually mimic the normal effects of insulin after eating. Patients, then, can vary their meal times with this drug. (Nateglinide appears to work more quickly and is shorter-acting than repaglinide). These agents may be particularly effective in combination with metformin or other agents. And they may be good agents for people with potential kidney problems.

Side Effects. Side effects include diarrhea and headache. As with the sulfonylureas, repaglinide poses a slightly increased risk for cardiac events. (Newer agents, such as nateglinide, may pose less of a risk.) People with heart failure or liver disease should use them with caution and be monitored.
Thiazolidinedione

Thiazolidinediones include rosiglitazone (Avandia) and pioglitazone (Actos). They improve insulin sensitivity by activating certain genes involved in fat synthesis and carbohydrate metabolism. These drugs are usually taken once or twice per day; however, it may take several days before the patient notices any results from them and several weeks before they take full effect. Thiazolidinediones do not cause hypoglycemia when used alone, although they are usually taken in combination with oral agents or insulin.

In some studies, thiazolidinediones have produced favorable effects on the heart, including reducing blood pressure and preventing blood clots. Pioglitazone improves triglyceride and HDL levels. (Rosiglitazone has mixed effects on lipid levels.) Of importance, some evidence suggests that these agents may preserve beta-cell function and, if used early, may help prevent progression of diabetes. This effect has not been observed with other standard oral agents.

Side Effects Nevertheless, thiazolidinediones can have serious side effects. They tend to increase fluid-build up, which can cause or worsen heart failure in some patients. Combinations with insulin increase the risk. They should not be used at all in patients with existing heart failure and should be used cautiously in those with risk factors for heart failure. Any patient who experiences sudden weight gain, water retention, or shortness of breath should call their physicians immediately.

Thiazolidinediones can cause also anemia and, as with other oral agents, can cause moderate weight gain. There have been a few reports of liver injury. At this time some experts believe thiazolidinediones should not be used routinely for managing type 2 diabetes but only in the context of clinical studies.
Alpha-Glucosidase Inhibitors

Alpha-glucosidase inhibitors, including acarbose (Precose, Glucobay) and miglitol (Glyset) reduce glucose levels by interfering with the absorption of starch in the small intestine. Acarbose tends to lower insulin levels after meals, a particular advantage, since higher levels of insulin after meals are associated with an increased risk for heart disease. Some evidence suggests that early use of these agents may reduce heart risk factors, including high blood pressure. A 2002 study using acarbose also suggested that these agents might even delay the development of type 2 diabetes in high-risk individuals. Alpha-glucosidase inhibitors are not as effective alone as other single oral drugs, but combinations, such as with metformin, insulin, or a sulfonylurea, increase their effectiveness.

Side Effects. These medications need to be taken with meals. Unfortunately, about a third of patients to stop taking the drug because of flatulence and diarrhea, particularly after high-carbohydrate meals. The drug may also interfere with iron absorption.

Alpha-glucosidase inhibitors do not cause hypoglycemia when used alone, but combinations with other drugs do. In such cases, it is important that the patient receive a solution that contains glucose or lactose, not table sugar. This is because acarbose inhibits the breakdown of complex sugar and starches, which includes table sugar.
Insulin Replacement

Issues Involves with Insulin Replacement. Insulin replacement is the best treatment for strict control of blood glucose and is required as natural insulin reserves are depleted. Because type 2 diabetes is progressive, most patients eventually require insulin, typically starting it in combination with an oral agent. However, when a single oral agent fails to control blood sugar it is not clear whether it is better to add insulin replacement or to add a second or third oral agent. A 2003 study reported that three oral agents were as effective as insulin plus an oral agent, but the costs are significantly higher. Some experts advocate using insulin as early as possible for optimal control.

However, in patients who still have insulin reserves, there is some concern that extra natural insulin will have adverse effects, including hypoglycemia, weight gain, and heart complications. It is still not clear if insulin replacement will improve survival rates compared to oral agents, notably metformin.

One approach that might solve some of these problems is to combine insulin with metformin, which achieves blood glucose control without added weight gain. Newer forms of insulin analogues, such as glargine, may be specifically helpful for people with type 2 diabetes and reduce the risk for hypoglycemia.

Fortunately, studies to date have not reported any adverse cardiac effects in patients with type 2 diabetes who are taking insulin. In fact, insulin has been associated, in some cases, with improvement in heart risk factors. More research is needed to clarify these important issues.

Forms of Insulin. Experts are working toward administering insulin so that it closely mimics the daily pattern of insulin, which responds to blood sugar levels by surging after meals and then falling to a steady base level afterward. To achieve this, physicians may use two insulin types:

* Fast-Acting Insulins for Surges. Insulin lispro and insulin aspart are fast-acting insulins. They mimic insulin's response to food intake. They are taken before meals, and their short action reduces the risk for hypoglycemia afterward.
* Slower Insulins for Base Levels. Intermediate forms (including NPH and lente) and long-acting forms (insulin glargine, ultralente insulin) have been developed to provide a steady level of insulin throughout the day. To date, glargine (Lantus) seems to be the most successful in achieving this goal in type 2 diabetes.

Noninjected forms of insulin are under investigation and may be particularly beneficial for type 2 diabetes. For example, preprandial inhaled insulin, or INH, is used with an inhaler, and Oralin is administered using an oral spray that is absorbed in the cheek lining. In one study, INH was added to oral agents administration and inhaled before meals. After 12 weeks it was more effective in controlling blood glucose, although patients gained weight and had a great incidence in hypoglycemia.

[For more detailed information on insulin therapy, see Well-Connected Report #9, Diabetes: Type 1.]
Investigative Agents

Incretins. Incretins are hormones that are released from the intestine and enhance insulin secretion. Glucagon-like insulinotropic peptide, or GLP-1 (Betatropin), is an incretin under investigation. It appears to help metabolize glucose and reduce appetite. Betatropin is administered using injections. Early studies report that it is effective in controlling blood glucose levels and has also been associated with weight reduction. A transmucosal tablet (placed between the lip and gum) is also under investigation and is showing benefits.

Pramlintide. Pramlintide (Symlin), known as an amylin analog, is derived from a natural hormone that acts in concert with the body's insulin in the pancreas to control hyperglycemia. It slows stomach emptying and delays absorption of nutrients in the intestine. It therefore prevents the surge in blood sugar that typically occurs after meals. Some studies indicate that in combination with insulin it helps control glucose levels, importantly after meals, without increasing the risk for hypoglycemia or increasing weight when added to insulin regimens. It is being considered for approval for both type 1 and type 2 insulin-dependent diabetes. One possible adverse effect is a delay in stomach emptying, which is already a complication of diabetes in some patients with neuropathy.

D-Chiro-Inositol. D-chiro-inositol (INS-1) is an investigational agent that increases sensitivity to insulin. It is showing promise in treating people with less severe diabetes and women with polycystic ovary syndrome. More research is underway.

Ciliary Neurotrophic Factor. An agent derived from ciliary neurotrophic factor (Axokine) signals the brain to suppress appetite. It is proving to be effective in achieving weight loss, and also improves cholesterol, lipid, and glucose levels regardless of food intake. The agent, then, may be particularly helpful for people with type 2 diabetes. It is currently in late trials.

Exenatide. Exenatide (Heloderma) is derived from the venom of the Gila monster. Animal and laboratory studies suggest that it enhances insulin secretion and slows stomach emptying. It may also have some protective effects on beta cells. Early studies are reporting reductions in HbA1C when used in combination with metformin, sulfonylureas, or both.

Glucovance

2008-07-09T03:16:00.001-07:00

Drug Description
DESCRIPTION

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 molec-ular weight of 494.01. The glyburide used in GLUCOVANCE has a particle size distribution of 25% undersize value not more than 6 m, 50% undersize value not more than 7 -10 m, and 75% undersize value not more than 21 m.

Metformin hydrochloride is an oral antihyperglycemic drug used in the management of type 2 dia-betes. Metformin hydrochloride (N, N-dimethylimidodicarbonimidic diamide monohydrochloride) is not chemically or pharmacologically related to sulfonylureas, thiazolidinediones, or -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 magne-sium stearate. The tablets are film coated, which provides color differentiation.

Glyburide

2008-07-09T03:14:00.001-07:00

GENERIC NAME: glyburide
BRAND NAMES: Micronase, Diabeta, Glynase

DRUG CLASS AND MECHANISM: Glyburide is an oral glucose lowering-drug in a class of diabetes medicines called sulfonylureas. Glyburide lowers the sugar level by stimulating insulin secretion in the pancreas. Insulin is a hormone which lowers the blood sugar level.

Approximately 90% of patients with diabetes have type 2 or non-insulin dependent diabetes mellitus. Type 2 diabetes usually occurs in adulthood, and is associated with obesity and a strong family history of the disease. Sugar (glucose) intolerance is related to impaired insulin secretion by the pancreas and resistance to insulin at the cell level.

PRESCRIPTION: Yes

GENERIC AVAILABLE: Yes

PREPARATIONS: Tablets; 1.25mg, 1.5mg, 2.5mg, 3mg, 5mg.

STORAGE: Glyburide should be stored at room temperature in a tight container.

PRESCRIBED FOR: Glyburide is used in type 2 diabetes to help lower and control blood sugars in those not controlled by diet alone. Studies have shown that strict sugar control in diabetics decreases the risks of eye, kidney, and nerve damage. Oral sulfonylureas are used in type 2 diabetics after a trial on a strict diabetic diet and usually before insulin is tried.

DOSING: Glyburide may be taken with or without food. Since glyburide is metabolized by the liver and excreted by the kidneys, dosages may need to be lowered in patients with liver or kidney dysfunction.

DRUG INTERACTIONS: All sulfonylureas can cause low blood sugar (hypoglycemia). Therefore, glyburide must be used cautiously in patients with kidney or liver problems, and those with poor food intake, using alcohol, or participating in heavy exercise, as well as in patients taking other glucose-lowering drugs. Drug interactions causing hypoglycemia can occur with nonsteroidal anti-inflammatories, sulfa drugs, coumadin, miconazole, fluoroquinolone antibiotics, and beta-blocking drugs. High glucose reactions (hyperglycemia) can occur with thiazide diuretics, corticosteroids, thyroid medicines, estrogens, niacin, dilantin, and calcium channel blocking drugs.

PREGNANCY: Glyburide is not recommended during pregnancy. Use of glyburide during the 2nd and 3rd term of pregnancy does not appear to affect the fetus, but use of glyburide during pregnancy should be discussed with a physician

NURSING MOTHERS: Glyburide should not be used by breast-feeding mothers.

SIDE EFFECTS: Minor side effects include nausea, heartburn, and bloating. Skin rashes can occur and cause itching, hives, or a diffuse measles-like rash. Rare but serious side effects include hepatitis, jaundice, and a low sodium concentration.

Glyburide Effective for Managing Gestational Diabetes

2008-07-09T03:12:00.000-07:00

Glyburide may control gestational diabetes unresponsive to diet therapy.

According to a new report. "Glyburide is a reasonable alternative to insulin therapy for women diagnosed with gestational diabetes and who fulfill the criteria we used in our study," says,Dr. Gavin F. Jacobson.

Dr. Jacobson, from Kaiser Permanente Northern California, San Francisco, and colleagues compared glyburide and insulin treatment in nearly 600 women with singleton pregnancies who had gestational diabetes diagnosed by oral glucose tolerance test between 12 and 34 weeks gestation, a fasting plasma glucose of 140 mg/dL or less, and who failed diet therapy.

Women treated with glyburide had significantly lower mean fasting and postprandial blood sugar levels, the authors report in the July issue of the American Journal of Obstetrics and Gynecology. Maternal hypoglycemia was rare with both treatments but more common in the glyburide group (0.20%) than in the insulin group (0.08%).

Twenty-eight women (12%) in the glyburide group were switched to insulin, the report indicates, including 14 for poor control and 8 for side effects attributed to hypoglycemia.

Most maternal and neonatal outcomes were similar between treatments, the researchers note. Preeclampsia was more common in the glyburide group, and neonates in the glyburide group were more likely to receive phototherapy.

Neonates in the insulin group, however, were more likely to be admitted to the neonatal intensive care unit, the results indicate. There were no neonatal deaths, lethal anomalies, or exchange transfusions in either treatment group, the investigators report. Four infants in each group had congenital anomalies.

"Women should be switched to insulin if they are unable to achieve adequate glycemic control on glyburide," Dr. Jacobson advised.

Also, he emphasized, "It is important women (treated with glyburide) receive all the other standard prenatal, intrapartum, and postpartum care that would have been provided if they were on insulin, including frequency of visits, counseling, and antenatal surveillance."

The study findings show that "glyburide can be used to achieve good glycemic control in a large clinical setting in the majority of women with gestational diabetes unresponsive to dietary management," write Dr. Celeste Durnwald and Dr. Mark B. Landon from The Ohio State University Medical Center, Columbus, in a related editorial. "Larger trials will also be of benefit in describing clinical characteristics associated with glyburide failure."

Dr. Jacobson added: "We are currently looking at the use of glyburide to treat a subgroup of women diagnosed with gestational diabetes in a nontraditional manner, specifically women diagnosed by a very high 1 hour GLT (>200mg/dl) and an elevated fasting (>105 mg/dl),"

Glucovance Oral

2008-06-20T09:55:00.001-07:00

This anti-diabetic medication is a combination of 2 drugs (glyburide and metformin). It is used along with a diet and exercise program to control high blood sugar in patients with type 2 diabetes (non-insulin-dependent diabetes).

Glyburide is a sulfonylurea and works by stimulating the release of your body's natural insulin and by decreasing the amount of sugar that your liver makes. Metformin is a biguanide and works by decreasing the amount of sugar that your liver makes and that your stomach/intestines absorb. Both of these medications work by helping to restore your body's proper response to the insulin you naturally produce.

Controlling high blood sugar helps prevent heart disease, strokes, kidney disease, blindness, circulation problems, and sexual function problems.
How To Use Glucovance Oral

Read the Patient Information Leaflet available from your pharmacist before you start using this medication and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth, usually once or twice a day with meals or as directed by your doctor. Drink plenty of fluids while taking this medication unless otherwise directed by your doctor.

The dosage is based on your medical condition and response to therapy. Your doctor may direct you to take a low dose at first, gradually increasing the dose to lower the chance of side effects such as upset stomach and low blood sugar. Your doctor will adjust your dose based on your blood sugar levels to find the best dose for you. Follow your doctor's directions carefully. The usual maximum dose for adults is 2000 milligrams of metformin and 20 milligrams of glyburide each day.

If you are already taking another anti-diabetic drug (e.g., chlorpropamide), follow your doctorâ€™s directions carefully for stopping the old drug and starting this combination medication.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same time(s) each day.

Inform your doctor if your condition persists or worsens (e.g., high/low blood sugar levels). It may take up to 2 weeks before the full benefit of this drug takes effect.

Metformin

2008-06-20T09:50:00.001-07:00

May Cause

2008-06-06T07:55:00.000-07:00

This medication may cause changes in your blood sugar. You should know the symptoms of low and high blood sugar and what to do if you have these symptoms.

You may experience hypoglycemia (low blood sugar) while you are taking this medication. Your doctor will tell you what you should do if you develop hypoglycemia. He or she may tell you to check your blood sugar, eat or drink a food or beverage that contains sugar, such as hard candy or fruit juice, or get medical care. Follow these directions carefully if you have any of the following symptoms of hypoglycemia:

* shakiness
* dizziness or lightheadedness
* sweating
* nervousness or irritability
* sudden changes in behavior or mood
* headache
* numbness or tingling around the mouth
* weakness
* pale skin
* hunger
* clumsy or jerky movements

If hypoglycemia is not treated, severe symptoms may develop. Be sure that your family, friends, and other people who spend time with you know that if you have any of the following symptoms, they should get medical treatment for you immediately.

* confusion
* seizures
* loss of consciousness

Call your doctor immediately if you have any of the following symptoms of hyperglycemia (high blood sugar):

* extreme thirst
* frequent urination
* extreme hunger
* weakness
* blurred vision

If high blood sugar is not treated, a serious, life-threatening condition called diabetic ketoacidosis could develop. Call your doctor immediately if you have any of these symptoms:

* dry mouth
* upset stomach and vomiting
* shortness of breath
* breath that smells fruity
* decreased consciousness

Glyburide may cause side effects. If you experience any of the following symptoms, call your doctor immediately:

* skin rash
* itching or redness
* exaggerated sunburn
* yellowing of the skin or eyes
* light-colored stools
* dark urine
* unusual bleeding or bruising
* fever
* sore throat

Glyburide Warnings

2008-06-06T07:49:00.000-07:00

Glyburide Warnings
Here are some additional precautions you should be aware of before taking glyburide.

* Tell your doctor if you have ever had unusual or allergic reactions to medications, especially to glyburide or to any sulfa medication, including sulfonamide antibiotics, diuretics (water pills), or other oral antidiabetics.

* Tell your doctor if you now have or ever had kidney disease, liver disease, thyroid disease, or a severe infection.

* Follow the special dietary instructions that your doctor gave you. This is an important part of controlling your blood sugar levels and is necessary for this medicine to work properly.

* Avoid drinking alcoholic beverages while taking this medication (unless otherwise directed by your doctor). Some patients who take this medicine experience nausea, vomiting, dizziness, stomach pain, pounding headache, sweating, and redness of the face and skin when they drink alcohol, and large amounts of alcohol can lower blood sugar to dangerously low levels.

* Be sure to tell your doctor or dentist that you are taking this medication before having any kind of surgery or other medical or dental treatment.

* Test for sugar in your urine as directed by your doctor. It is a convenient way to determine whether or not your diabetes is being controlled by this medicine.

* Eat or drink something containing sugar right away if you experience any symptoms of low blood sugar (such as anxiety, chills, cold sweats, cool or pale skin, drowsiness, excessive hunger, headache, nausea, nervousness, rapid heartbeat, shakiness, or unusual tiredness or weakness). It is also important that your family and friends recognize the symptoms of low blood sugar and know what to do if they observe any of these symptoms in you. Also, check with your doctor as soon as possible -- even if these symptoms are corrected by the sugar. The blood-sugar-lowering effects of this medicine can last for hours, and the symptoms may return during this period. Good sources of sugar are orange juice, corn syrup, honey, sugar cubes, and table sugar. You are at greatest risk of developing low blood sugar if you skip or delay meals, exercise more than usual, cannot eat because of nausea or vomiting, or drink large amounts of alcohol.

* Be sure to tell your doctor if you are pregnant. Studies of this drug taken in human pregnancy have not yet been completed, but studies in animals have shown it can cause birth defects. Consult your doctor if you are nursing an infant.

What side effects may I notice from taking glyburide

2008-06-06T07:43:00.002-07:00

Side effects that you should report to your prescriber or health care professional as soon as possible:
•hypoglycemia (low blood glucose) which can cause symptoms such as anxiety or nervousness, confusion, difficulty concentrating, hunger, pale skin, nausea, fatigue, perspiration, headache, palpitations, numbness of the mouth, tingling in the fingers, tremors, muscle weakness, blurred vision, cold sensations, uncontrolled yawning, irritability, rapid heartbeat, shallow breathing, and loss of consciousness.
•breathing difficulties, severe skin reactions or excessive phlegm, which may indicate that you are having an allergic reaction to the drug.
•dark yellow or brown urine, or yellowing of the eyes or skin, indicating that the drug is affecting your liver.
•fever, chills, sore throat; which means the drug may be affecting your immune system.
•unusual bleeding or bruising; which occurs when the drug is affecting your blood clotting system.

Side effects that usually do not require medical attention (report to your prescriber or health care professional if they continue or are bothersome):
•headache
•heartburn, stomach discomfort
•increased sensitivity to the sun
•nausea, vomiting
•skin rash, redness, swelling or itching

Interact with Glyburide

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•alcohol
•beta-blockers (used for high blood pressure or heart conditions)
•bosentan (bosentan should not be taken with glyburide, contact your prescriber)
•cisapride
•clofibrate
•diazoxide
•medicines for fungal or yeast infections (examples: fluconazole, itraconazole, miconazole, voriconazole)
•metoclopramide
•rifampin
•warfarin (a blood thinner)

Many medications may cause changes (increase or decrease) in blood sugar, these include:
•alcohol containing beverages
•aspirin and aspirin-like drugs
•beta-blockers, often used for high blood pressure or heart problems (examples include atenolol, metoprolol, propranolol)
•chromium
•female hormones, such as estrogens or progestins, birth control pills
•isoniazid
•male hormones or anabolic steroids
•medications for weight loss
•medicines for allergies, asthma, cold, or cough
•niacin
•pentamidine
•phenytoin
•quinolone antibiotics (examples: ciprofloxacin, levofloxacin, ofloxacin)
•some herbal dietary supplements
•steroid medicines such as prednisone or cortisone
•thyroid hormones
•water pills (diuretics)

Tell your prescriber or health care professional about all other medicines you are taking, including non-prescription medicines, nutritional supplements, or herbal products. Also tell your prescriber or health care professional if you are a frequent user of drinks with caffeine or alcohol, if you smoke, or if you use illegal drugs. These may affect the way your medicine works. Check with your health care professional before stopping or starting any of your medicines.

Precautions

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Before taking glyburide,

* tell your doctor and pharmacist if you are allergic to glyburide or any other drugs.
* tell your doctor and pharmacist what prescription and nonprescription medications you are taking, especially antibiotics, anticoagulants ('blood thinners') such as warfarin (Coumadin), dexamethasone (Decadron), diuretics ('water pills'), estrogens, isoniazid (INH), MAO inhibitors [phenelzine (Nardil) and tranylcypromine (Parnate)], medications for high blood pressure or heart disease, metformin (Glucophage), niacin (nicotinic acid), oral contraceptives, phenytoin (Dilantin), prednisone, probenecid (Benemid), and vitamins.
* tell your doctor if you have or have ever had heart or kidney disease.
* tell your doctor if you are pregnant, plan to become pregnant, or are breast-feeding. If you become pregnant while taking glyburide, call your doctor.
* if you are having surgery, including dental surgery, tell the doctor or dentist that you are taking glyburide.
* you should know that this drug may make you drowsy. Do not drive a car or operate machinery until you know how this drug affects you.
* remember that alcohol can add to the drowsiness caused by this drug.
* tell your doctor if you use tobacco products. Cigarette smoking may decrease the effectiveness of glyburide.
* plan to avoid unnecessary or prolonged exposure to sunlight and to wear protective clothing, sunglasses, and sunscreen. Glyburide may make your skin sensitive to sunlight.

Precautions

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What are Glyburide Tablets

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GLYBURIDE (Diabeta®, Glynase™, Micronase®) helps to treat type 2 diabetes mellitus. Treatment is combined with a suitable diet and balanced exercise. Glyburide increases the amount of insulin released from the pancreas and helps your body to use insulin more efficiently. Generic glyburide tablets are available.

Pregnancy Implications

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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

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

Glyburide Synonyms

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Diabeta; Glibenclamide; Glybenclamide; Glybenzcyclamide

U.S Brand Name Glyburide

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Dia eta®; Glynase® PresTab®; Micronase®

New Classification

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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

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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

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Types:

There are three types of 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:

Insulin resistance in the muscle tissue, causing the muscles to take up less glucose from the blood.
Impaired insulin secretion by the pancreas.
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

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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

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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

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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

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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

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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

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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.