glibenclamide is indicated for the treatment of mild to moderate type 2 diabetes that is not adequately controlled by diet alone, in patients whose pancreatic β-cells still possess some insulin-secreting capability and who do not have severe complications.
Dosage and Administration:
Oral administration, starting with 2.5mg (1 tablet) before breakfast or once before breakfast and once before lunch. For mild cases, 1.25mg (half a tablet) three times a day, before meals, increasing to 2.5mg (1 tablet) daily after 7 days. The usual dosage is 5-10mg per day (2-4 tablets daily), with a maximum dosage not exceeding 15mg (6 tablets) per day.
Special Populations:
Pregnant and Nursing Women:
- Animal experiments and clinical observations have shown that sulfonylurea antidiabetic drugs can cause stillbirths and fetal malformations; therefore, they should not be taken by pregnant women.
- These drugs can be excreted through breast milk, and nursing mothers should not take them to avoid causing hypoglycemia in the infant.
Children:
No trials have been conducted, and there are no reliable references.
Elderly:
Elderly patients and those with renal impairment have reduced metabolism and excretion capabilities for these drugs, making glibenclamide’s hypoglycemic effect relatively stronger. It is not recommended for these populations, and other sulfonylureas with shorter action times should be used instead.
Adverse Reactions:
- May include diarrhea, nausea, vomiting, headache, stomach pain, or discomfort.
- Less commonly, rashes may occur.
- Rare but serious side effects include jaundice, liver function impairment, bone marrow suppression, neutropenia (manifested by sore throat, fever, infection), and thrombocytopenia (manifested by bleeding, purpura).
Contraindications:
- Patients with type 1 diabetes.
- Patients with type 2 diabetes who have ketoacidosis, coma, severe burns, infections, trauma, and major surgery, or other stress conditions.
- Those with liver or kidney impairment.
- Those allergic to sulfonamides.
- Patients with leukopenia.
Drug Interactions:
- Concurrent use with alcohol can cause abdominal cramps, nausea, vomiting, headache, facial flushing, and hypoglycemia.
- Concomitant use with β-blockers may increase the risk of hypoglycemia and can mask symptoms of hypoglycemia, such as increased pulse rate and blood pressure; the likelihood of this happening with selective β-blockers like atenolol and metoprolol is smaller.
- Chloramphenicol, guanethidine, insulin, monoamine oxidase inhibitors, cortisone, hydrocortisone, bumetanide, salicylates, sulfonamides used concurrently with this drug can enhance the hypoglycemic effect.
- Corticosteroids, epinephrine, phenytoin, thiazide diuretics, thyroid hormones can increase blood glucose levels; when used with this class of drugs, the dosage may need to be increased.
- Coumarin anticoagulants used concurrently with this class of drugs initially increase each other’s plasma concentrations, but later decrease them, thus requiring dosage adjustments for both.
glibenclamide and Glimepiride have several key differences, which affect their dosing regimens and overall efficacy:
First, the duration of action differs between the two, leading to different administration methods. glibenclamide, a second-generation sulfonylurea, is considered a short-acting sulfonylurea. It typically needs to be taken three times a day, usually before meals. The daily dosage is around 7.5 mg, with a recommendation not to exceed 15 mg per day for diabetics to avoid potential side effects. Glimepiride, a third-generation sulfonylurea, is a longer-acting medication and only needs to be taken once a day, usually before the first meal of the day, which could be before or after breakfast. The recommended daily dosage ranges from 2 to 4 mg.
Second, the onset of action and intensity of effect also differ between the two. Short-acting glimepiride generally has a more rapid effect and a stronger hypoglycemic action. However, glimepiride has a longer duration of action and a more gentle profile, also regulating fasting blood glucose and improving insulin resistance, making its effects more favorable and defined.
Third, the incidence of hypoglycemia varies between the two. All sulfonylureas can cause hypoglycemia, but glimepiride has a lower risk of hypoglycemia with a single dose compared to glibenclamide. The impact on weight gain also differs, with glibenclamide having a more significant effect on obese patients, while glimepiride has a smaller impact.
Management of Overdose:
Signs of overdose:
An overdose of sulfonylureas (including glibenclamide tablets) can result in hypoglycemia.
Treatment approach:
Mild hypoglycemia without loss of consciousness or neurological symptoms should be actively treated with oral glucose and adjustment of the medication dose and/or dietary pattern. Close monitoring should continue until the physician is confident that the patient is out of danger. Severe hypoglycemic reactions with coma, seizures, or other neurological disabilities are rare but require immediate hospital treatment if they occur. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of concentrated (50%) glucose solution, followed by continuous infusion of a more dilute (10%) glucose solution to maintain blood glucose above 100 mg/dL. The patient should be closely monitored for at least 24-48 hours because hypoglycemia may recur after apparent clinical recovery.
Who should be cautious about the risk of severe hypoglycemia?
All sulfonylureas can cause severe hypoglycemia. Proper patient selection and dosing instructions are important to avoid hypoglycemic episodes. Impaired renal or liver function may lead to increased drug levels of glibenclamide and may also reduce gluconeogenesis, both of which increase the risk of severe hypoglycemic reactions. Elderly, frail, or malnourished patients, as well as those with adrenal or pituitary insufficiency, are particularly susceptible to the hypoglycemic effects of antidiabetic medications. Hypoglycemia may be difficult to recognize in the elderly and in those taking β-adrenergic blockers. Hypoglycemia is more likely to occur with inadequate calorie intake, after strenuous or prolonged exercise, with alcohol consumption, or when combining more than one antidiabetic medication, which may increase the risk of hypoglycemia.
Some well-known pharmaceutical companies that produce glibenclamide include:
- Merck: The brand names for glibenclamide produced by Merck are Januvia and Janumet.
- AstraZeneca: The brand name for glibenclamide produced by AstraZeneca is Onglyza.
- MSD: The brand name for glibenclamide produced by MSD is Sitagliptin.
- Novartis: The brand name for glibenclamide produced by Novartis is Galvus.