Metformin vs. Glucovance

• Metformin and Glucovance (glyburide/metformin) are antidiabetic medications used to treat type 2 diabetes in adults and children.
• Glucovance contains metoformin along with another medication, glyburide.
• Brand names for Metformin include Glucophage, Glucophage XR, Glumetza, Fortamet, and Riomet.
• Side effects of Metformin and Glucovance that are similar include nausea, vomiting, gas, diarrhea, decreased appetite, low blood glucose, and heartburn.
• Side effects of Metformin that are different from Glucovance include bloating, weakness, respiratory tract infections, low levels of vitamin B-12, and chills.
• Side effects of Glucovance that are different from Metformin include stomach pain, upset stomach, headache, dizziness, metallic taste, and weight loss.

• Metformin is used for treating type 2 diabetes in adults and children. It may be used alone or in combination with other diabetic medications. Metformin also has been used to prevent the development of diabetes in people at risk for diabetes, treatment of polycystic ovaries, and weight gain due to medications used for treating psychoses.
  • Metformin is an oral biguanide antidiabetic agent. It decreases the production of glucose in the liver, decreases the absorption of glucose by the intestines, and increases the uptake and use of blood glucose by cells throughout the body.
• Glucovance (glyburide/metformin) is a combination antidiabetic medication containing glyburide and metformin. Glucovance is used to improve blood glucose (sugar) control in adults with type 2 diabetes mellitus.
  • Glyburide is a second-generation oral sulfonylurea. It helps to lower blood glucose by stimulating the release of insulin, the hormone responsible for regulating blood glucose. In clinical studies, glyburide/metformin therapy was observed to be superior in improving fasting plasma glucose, post-meal blood glucose, and HbA1c levels versus treatment with glyburide or metformin alone.

Metformin side effects

The most common side effects with metformin are:

• nausea,
• vomiting,
• gas,
• bloating,
• diarrhea and
• loss of appetite.

These symptoms occur in one out of every three patients. These side effects may be severe enough to cause therapy to be discontinued in one out of every 20 patients. These side effects are related to the dose of the medication and may decrease if the dose is reduced.

Metformin may also cause:

• weakness,
• respiratory tract infections,
• low levels of vitamin B-12,
• low blood glucose,
• heartburn, and
• chills.

A serious but rare side effect of metformin is lactic acidosis. Lactic acidosis occurs in one out of every 30,000 patients and is fatal in 50% of cases. The symptoms of lactic acidosis are:

• weakness,
• trouble breathing,
• abnormal heartbeats,
• unusual muscle pain,
• stomach discomfort,
• light-headedness, and
• feeling cold.

Patients at risk for lactic acidosis include those with reduced function of the:

• kidneys or liver,
• congestive heart failure,
• severe acute illnesses, and
• dehydration.

Glucovance side effects

The most common side effects include:

• stomach pain,
• diarrhea,
• upset stomach,
• nausea,
• vomiting,
• headache, and
• dizziness.

Other commonly reported side effects with Glucovance therapy include:

• decreased appetite,
• metallic taste,
• gas,
• heartburn, and
• weight loss.

Other side effects include:

• hypoglycemia (low blood glucose),
• blood disorders,
• decrease blood sodium levels,
• rash,
• sensitivity to the sunlight,
• itching,
• liver disease,
• SIADH,
• hives, and
• hypersensitivity type reactions.

Metformin can cause a rare but serious condition known as lactic acidosis, a build-up of acid in the blood. Lactic acidosis can cause death and requires immediate treatment. Symptoms of lactic acidosis include:

• tiredness,
• weakness,
• unusual
• muscle pain,
• pain in the stomach,
• difficulty breathing,
• dizziness, and
• slow or irregular heartbeat.

Patients suspected of having signs or symptoms of lactic acidosis must seek emergency medical help.

Metformin dosage

• For treating type 2 diabetes in adults, metformin (immediate release) usually is begun at a dose of 500 mg twice a day or 850 mg once daily. The dose is gradually increased by 500 mg weekly or 850 mg every two weeks as tolerated and based on the response of the levels of glucose in the blood. The maximum daily dose is 2550 mg given in three divided doses.
• If extended tablets are used, the starting dose is 500 mg or 1000 mg daily with the evening meal. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg except for Fortamet (2500 mg of Fortamet, once daily or in two divided doses). Glumetza tablets (500 -1000mg formulations are given once daily (either 1000 to 2000mg). Fortamet and Glumetza are modified release formulations of metformin. Metformin should be taken with meals.
• For pediatric patients 10-16 years of age, the starting dose is 500 mg twice a day. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg in divided doses.
• Children older than 17 years of age may receive 500 mg of extended release tablets daily up to a maximum dose of 2000 mg daily. Extended release tablets are not approved for children younger than 17 years of age.
• Metformin-containing drugs may be safely used in patients with mild to moderate renal impairment. Renal function should be assessed before starting treatment and at least yearly.
• Metformin should not be used by patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m2 and starting metformin in patients with an eGFR between 30-45 mL/minute/1.73 m2 is not recommended.
• Metformin should be stopped at the time of or before administering iodinated contrast in patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Kidney function should be evaluated 48 hours after receiving contrast and metformin may be restarted if kidney function is stable.

Glucovance dosage

• For patients inadequately controlled on diet and exercise
  • Generally, the recommended starting dose of Glucovance is 1.25/250 mg administered once daily with a meal.
  • A starting dose of 1.25/ 250 mg twice daily may be considered for patients with HbA1c >9% or fasting plasma glucose (FPG) >200 mg/dL.
  • If necessary, dosage may be increased in increments of 1.25/250 mg at two week intervals.
  • The maximum daily dose of Glucovance is 20/2000 mg.
• For patients inadequately controlled on a sulfonylurea and/or metformin
  • Generally, the recommended starting dose of Glucovance is 2.5 mg/500 mg or 5 mg/500 mg orally twice a day with meals.
• Metformin-containing drugs may be safely used in patients with mild to moderate renal impairment. Renal function should be assessed before starting treatment and at least yearly.
• Metformin should not be used by patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m2 and starting metformin in patients with an eGFR between 30-45 mL/minute/1.73 m2 is not recommended.
• Metformin should be stopped at the time of or before administering iodinated contrast in patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast.
• Kidney function should be evaluated 48 hours after receiving contrast and metformin may be restarted if kidney function is stable.
• The safety and efficacy of Glucovance has not been established in pediatric patients. Therefore, use of Glucovance in this patient population is not recommended.

Metformin drug interactions

• Cimetidine (Tagamet), by decreasing the elimination of metformin from the body, can increase the amount of metformin in the blood by 40%. This may increase the frequency of side effects from metformin.
• Ioversol (Optiray) and other iodinated contrast media may reduce kidney function, which reduces elimination of metformin, leading to increased concentrations of metformin in the blood. Metformin should be stopped 48 hours before and after use of contrast media.
• Thiazide diuretics, steroids, estrogens, and oral contraceptives may increase blood glucose and reduce the effect of metformin. When these drugs are stopped, patients should be closely observed for signs of low blood glucose.
• Alcohol consumption increases the effect of metformin on lactate production, increasing the risk of lactic acidosis.

Glucovance drug interactions

• Drugs that cause blood glucose levels to increase may diminish the effectiveness of Glucovance therapy. When these drugs are stopped, patients should be closely observed for signs of low blood glucose. These drugs include
  • thiazides,
  • other diuretics,
  • corticosteroids,
  • phenothiazines,
  • thyroid medications,
  • estrogens,
  • birth control pills,
  • phenytoin (Dilantin),
  • nicotinic acid,
  • sympathomimetics,
  • calcium channel blockers (CCBs), and
  • isoniazid (Nydrazid).
• Cimetidine (Tagamet), by decreasing the elimination of metformin from the body, can increase the amount of metformin in the blood by 40%. This may increase the frequency of side effects from metformin.
• Contrast media used for radiological procedures may reduce kidney function which reduces elimination of metformin, leading to increased concentrations of metformin in the blood. Metformin should be stopped 48 hours before and after use of contrast media.
• Alcohol consumption increases the effect of metformin on lactate production, increasing the risk of lactic acidosis.
• Certain drugs may increase the blood glucose lowering actions of glyburide. It is possible that hypoglycemia (low blood glucose) and symptoms from hypoglycemia may result. Such drugs include
  • nonsteroidal anti-inflammatory medications (NSAIDs),
  • salicylates,
  • sulfonamides,
  • chloramphenicol,
  • probenecid,
  • coumarins,
  • ciprofloxacin (Cipro),
  • monoamine oxidase inhibitors (MAOIs),
  • oral miconazole, and
  • beta-adrenergic blockers.
• Coadministration of glyburide with bosentan (Tracleer) may cause an abnormal increase in liver enzymes. Therefore, concomitant use of these agents is not recommended.
• Colesevelam (Welchol) may reduce blood levels of glyburide. Patients are advised to take glyburide 1 hour before or 4 hours after colesevelam administration to minimize the risk of their interaction.

Metformin

• There are no adequate studies in pregnant women. Most experts agree that insulin is the best treatment for pregnant women with diabetes.
• Metformin is excreted into breast milk and can therefore be transferred to the nursing infant. Nursing mothers should not use metformin.

Glucovance

• Glucovance has not been adequately evaluated in pregnant women. Due to the lack of conclusive safety data, Glucovance should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Glucovance is classified as FDA pregnancy risk category B.
• It is not known if Glucovance is excreted in breast milk. Due to the lack of safety data and the potential risk for hypoglycemia (low blood glucose) in nursing infants, use of Glucovance in nursing mothers is not recommended.