====== Glyburide ======

Glyburide is a second-generation sulfonylurea that stimulates pancreatic insulin secretion.

It is associated with a higher risk of prolonged hypoglycemia compared to other sulfonylureas.

→ [[endocrine:sulfonylureas:start|Sulfonylureas]]

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===== Mechanism of Action =====

Glyburide binds to:

  * Sulfonylurea receptor (SUR1)
  * Component of the ATP-sensitive potassium (KATP) channel on pancreatic beta cells

Mechanism sequence:

  * KATP channel closure
  * Membrane depolarization
  * Calcium influx
  * Insulin release

Important:

  * Insulin secretion is NOT glucose-dependent
  * Hypoglycemia risk is significant

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===== Clinical Effects =====

  * Moderate HbA1c reduction
  * Weight gain
  * Higher risk of hypoglycemia compared to glipizide

Requires functional pancreatic beta cells.

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===== Pharmacokinetics =====

  * Longer duration of action
  * Hepatic metabolism
  * Active metabolites

Because metabolites are active, hypoglycemia may be prolonged — especially in renal impairment.

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===== Adverse Effects =====

Common:

  * Hypoglycemia
  * Weight gain

Severe risk:

  * Prolonged hypoglycemia
  * Increased risk in elderly
  * Increased risk in CKD

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===== Contraindications / Cautions =====

Avoid in:

  * Elderly patients
  * Renal impairment
  * History of severe hypoglycemia

Caution in:

  * Irregular meal patterns
  * Alcohol use

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===== Glyburide vs Other Sulfonylureas =====

Compared to:

  * [[endocrine:sulfonylureas:glipizide|Glipizide]] → higher hypoglycemia risk
  * [[endocrine:sulfonylureas:glimepiride|Glimepiride]] → higher hypoglycemia risk

Glipizide is generally preferred in older adults and CKD.

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===== Special Considerations =====

Glyburide has been studied in gestational diabetes.

However, insulin remains the preferred therapy in pregnancy.

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===== Glyburide vs Other Diabetes Agents =====

Compared to:

  * [[endocrine:biguanides:metformin|Metformin]] → more hypoglycemia, more weight gain
  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]] → no weight loss, no ASCVD benefit
  * [[endocrine:sglt2:start|SGLT2 Inhibitors]] → no heart failure benefit

Sulfonylureas are inexpensive but lack cardioprotective benefit.

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===== Clinical Pearls =====

  * Second-generation sulfonylurea
  * Active metabolites
  * Higher risk of prolonged hypoglycemia
  * Avoid in elderly and CKD
  * Weight gain common
  * Less preferred in modern practice

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===== Related =====

  * [[endocrine:sulfonylureas:start|Sulfonylureas]]
  * [[endocrine:sulfonylureas:glipizide|Glipizide]]
  * [[endocrine:sulfonylureas:glimepiride|Glimepiride]]
  * [[endocrine:biguanides:metformin|Metformin]]