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Glyburide (Glibenclamide) /​ Metformin

    DEA Class; Rx

    Common Brand Names; Glucovance

    • Antidiabetics, Sulfonylureas/Biguanides

    Oral combination of metformin with a ‘second-generation’ sulfonylurea
    Used in adults for type 2 diabetes mellitus; due to longer duration of action, glyburide is not preferred in the elderly
    Risk of lactic acidosis from metformin is low but requires care in monitoring

    Indicated for the treatment of type 2 diabetes mellitus not controlled by diet and exercise alone.

    For use when either glyburide or metformin alone do not result in adequate glycemic control.

    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 <30 ml/min/1.73 m²

    • Dermatologic reactions
    • Heartburn
    • Hypoglycemia
    • Nausea/vomiting
    • Gastrointestinal: Cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure; discontinue drug
    • Allergic: Angioedema, arthralgia, myalgia, and vasculitis
    • Dermatologic: Porphyria cutanea tarda and photosensitivity
    • Hematologic: Leukopenia, agranulocytosis, thrombocytopenia, which occasionally may present as purpura, hemolytic anemia, aplastic anemia, and pancytopenia
    • Metabolic: Hepatic porphyria reactions reported with sulfonylureas but not with glyburide; disulfiram-like reactions reported very rarely with glyburide; cases of hyponatremia reported most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone
    • Liver function abnormalities, including isolated transaminase elevations (glyburide)

    If metformin-associated lactic acidosis 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 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, drug should be discontinued

    Use with caution in patients with 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


    Withholding of food and fluids during surgical or other procedures may increase 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 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

    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 placenta and have been associated with neonatal adverse reactions such as hypoglycemia

    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


    Glyburide 20 mg/day PO; metformin 2,000 mg/day PO. Use lower doses in debilitated patients.


    Glyburide 20 mg/day PO; metformin 2,000 mg/day PO. Use lower doses in debilitated patients.


    Safety and efficacy have not been established.


    Safety and efficacy have not been established.



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