====== Glipizide ======

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

It is one of the most commonly used sulfonylureas.

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

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

Glipizide binds to:

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

Mechanism sequence:

  * Closure of KATP channel
  * Membrane depolarization
  * Opening of voltage-gated calcium channels
  * Increased intracellular calcium
  * Insulin release

Important:

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

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

  * Moderate HbA1c reduction
  * Rapid onset of action
  * Weight gain
  * Risk of hypoglycemia

Requires functional pancreatic beta cells.

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===== Pharmacokinetics =====

  * Shorter half-life than glyburide
  * Available in immediate-release and extended-release formulations
  * Primarily metabolized in the liver
  * Inactive metabolites

Glipizide is preferred over glyburide in patients with renal impairment due to lower hypoglycemia risk.

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

Common:

  * Hypoglycemia
  * Weight gain

Severe hypoglycemia risk increases with:

  * Elderly patients
  * Renal impairment
  * Irregular meal intake
  * Alcohol use

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===== Contraindications =====

  * Type 1 Diabetes
  * History of severe hypoglycemia
  * Caution in elderly
  * Caution in CKD

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===== Glipizide vs Other Sulfonylureas =====

Compared to:

  * [[endocrine:sulfonylureas:glyburide|Glyburide]] → lower hypoglycemia risk
  * [[endocrine:sulfonylureas:glimepiride|Glimepiride]] → similar efficacy

Glipizide is generally preferred over glyburide in older adults.

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===== Glipizide 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 effects.

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

  * Second-generation sulfonylurea
  * Closes beta-cell KATP channels
  * Hypoglycemia risk
  * Weight gain
  * Preferred over glyburide in CKD
  * Requires functioning beta cells

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===== Related =====

  * [[endocrine:sulfonylureas:start|Sulfonylureas]]
  * [[endocrine:sulfonylureas:glyburide|Glyburide]]
  * [[endocrine:sulfonylureas:glimepiride|Glimepiride]]
  * [[endocrine:biguanides:metformin|Metformin]]