Glyburide-Metformin

Glyburide-Metformin is a combination medication used for the treatment of type 2 diabetes mellitus.

• Glyburide-Metformin is available under the following different brand names: Glucovance

Common side effects of Glyburide-Metformin include:

• low blood sugar,
• nausea,
• diarrhea,
• upset stomach, and
• headache

Serious side effects of Glyburide-Metformin include: 

• hives,
• difficulty breathing,
• swelling of the face, lips, tongue, or throat,
• swelling,
• rapid weight gain,
• shortness of breath,
• extreme weakness,
• blurred vision,
• sweating,
• trouble speaking,
• tremors,
• stomach pain,
• confusion,
• seizures,
• unusual muscle pain,
• trouble breathing,
• stomach pain,
• vomiting,
• irregular heart rate,
• dizziness,
• feeling cold,
• weakness, and
• tiredness

Rare side effects of Glyburide-Metformin include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 1.25 mg/250 mg
• 2.5 mg/500 mg
• 5 mg/500 mg

Type 2 Diabetes Mellitus

Adult and geriatric dosage

• 1.25/250 mg Glyburide-Metformin orally every day or every 12 hours
• May titrate up at 2-week intervals; maximum 20/2000 mg/day

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Glyburide-Metformin has severe interactions with the following drug:
  • bosentan
• Glyburide-Metformin has serious interactions with the following drugs:
  • aminolevulinic acid oral
  • aminolevulinic acid topical
  • contrast media (iodinated)
  • darolutamide
  • eluxadoline
  • ethanol
  • fluvastatin
  • ioversol
  • ivosidenib
  • lasmiditan
  • lonafarnib
  • lumacaftor/ivacaftor
  • methyl aminolevulinate
  • methylene blue
• Glyburide-Metformin has moderate interactions with at least 347 other drugs.
• Glyburide-Metformin has minor interactions with at least 131 other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all your products. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Hypersensitivity to glyburide or metformin
• Congestive heart failure, metabolic acidosis
• Diabetic ketoacidosis, with or without coma (treat with insulin)
• Coadministration with bosentan (increased risk of hepatotoxicity)
• Severe renal disease: eGFR less than 30 ml/min/1.73 m²

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Glyburide-Metformin?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Glyburide-Metformin?”

Cautions

• If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of therapy; in patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin (metformin hydrochloride is dialyzable, with a clearance of up to170 mL/minute under good hemodynamic conditions); hemodialysis has often resulted in reversal of symptoms and recovery
• Allergic skin reactions, eg, pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions occur in 1.5% of glyburide-treated patients, which may be transient and may disappear despite continued use; if skin reactions persist, the drug should be discontinued
• Use with caution in patients with a risk of severe hypoglycemia: elderly, debilitated, or malnourished, adrenal or pituitary insufficiency
• Use with caution in patients with stress due to infection, fever, trauma, or surgery
• Before initiating therapy, obtain an estimated glomerular filtration rate
• Pregnancy/Lactation
• Withholding of food and fluids during surgical or other procedures may increase the risk for volume depletion, hypotension, and renal impairment; therapy should be temporarily discontinued while patients have restricted food and fluid intake
• Several of the postmarketing cases of metformin-associated lactic acidosis occurred in the setting of acute congestive heart failure (particularly when accompanied by hypoperfusion and hypoxemia); cardiovascular collapse (shock) acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia; discontinue therapy when such events occur
• Use with caution in patients with dehydration, heavy use of alcohol, hypoxic states, impaired hepatic or renal function
• Hemolytic anemia may occur with glucose 6-phosphate dehydrogenase (G6PD) deficiency when treated with sulfonylurea agents
• Clinical recommendations based on the patient’s renal function
  • Before initiating therapy, obtain an eGFR.
  • Initiation of therapy is not recommended in patients with eGFR between 30 –45 mL/minute/1.73 m²
  • Obtain an eGFR at least annually in all patients receiving therapy
  • In patients at increased risk for the development of renal impairment (e.g., the elderly), renal function should be assessed more frequently
  • If eGFR later falls below 45 mL/minute/1.73 m², assess the benefit and risk of continuing therapy
• Iodinated contrast imaging procedures
  • Discontinue metformin at the time of or before an iodinated contrast imaging procedure in patients with an eGFR between 30-60 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
  • Reevaluate eGFR 48 hours after the imaging procedure; restart metformin if renal function is stable

Pregnancy and Lactation

• Available data from a small number of published studies and postmarketing experience with glyburide use in pregnancy over decades have not identified any drug-associated risks for major birth defects, miscarriage, or adverse maternal outcomes; however, sulfonylureas (including glyburide) cross the placenta and have been associated with neonatal adverse reactions such as hypoglycemia; therapy should be discontinued at least two weeks before expected delivery
• Limited data with metformin in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage; published studies with metformin use during pregnancy have not reported a clear association between metformin and major birth defect or miscarriage risk; there are risks to mother and fetus associated with poorly controlled diabetes mellitus in pregnancy
• Poorly controlled diabetes mellitus in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications; poorly controlled diabetes mellitus increases the fetal risk for major birth defects, stillbirth, and macrosomia-related morbidity
• Neonates of women with gestational diabetes who are treated with sulfonylureas during pregnancy may be at increased risk for neonatal intensive care admission and may develop respiratory distress, hypoglycemia, birth injury, and be large for gestational age; prolonged severe hypoglycemia, lasting 4-10 days, has been reported in neonates born to mothers receiving a sulfonylurea at time of delivery and has been reported with the use of agents with a prolonged half-life; observe newborns for symptoms of hypoglycemia and respiratory distress and manage accordingly
• Due to reports of prolonged severe hypoglycemia in neonates born to mothers receiving a sulfonylurea at the time of delivery, therapy should be discontinued at least two weeks before the expected delivery
• Lactation
  • Breastfed infants of lactating women on therapy should be monitored for symptoms of hypoglycemia; although glyburide was negligible in human milk in one small clinical lactation study; this result is not conclusive because of limitations of assay used in the study; there are no data on effects of glyburide on milk production; limited published studies report that metformin is present in human milk; however, there is insufficient information to determine effects of metformin on the breastfed infant and no available information on effects of metformin on milk production; therefore, developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on the breastfed child from drug or from the underlying maternal condition
  • Monitor breastfed infants for signs of hypoglycemia (eg, jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, seizures)