====== Repaglinide ======

Repaglinide is a short-acting meglitinide that stimulates rapid insulin secretion to control postprandial glucose.

It is taken before meals and primarily targets postprandial hyperglycemia.

→ [[endocrine:meglitinides:start|Meglitinides]]

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

Repaglinide binds to:

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

Mechanism sequence:

  * Closure of KATP channel
  * Membrane depolarization
  * Calcium influx
  * Insulin release

Important:

  * Rapid onset
  * Short duration
  * Insulin secretion is NOT glucose-dependent
  * Lower risk of prolonged hypoglycemia than sulfonylureas

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

  * Modest HbA1c reduction
  * Strong postprandial glucose control
  * Mild weight gain
  * Reduced risk of prolonged hypoglycemia compared to sulfonylureas

Requires functioning beta cells.

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===== Dosing =====

  * Taken before each meal
  * Skip dose if meal is skipped
  * Flexible for irregular meal schedules

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===== Pharmacokinetics =====

  * Rapid absorption
  * Short half-life
  * Hepatic metabolism (CYP3A4 and CYP2C8)

Drug interactions are clinically relevant.

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===== Drug Interactions =====

CYP3A4 inhibitors may increase repaglinide levels.

Important interaction:

  * Gemfibrozil (CYP2C8 inhibitor) → significantly increases repaglinide concentration
  * Combination is generally avoided

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

Common:

  * Hypoglycemia (less severe than sulfonylureas)
  * Weight gain

Lower prolonged hypoglycemia risk compared to:

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

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

  * Type 1 Diabetes
  * Severe hepatic impairment

Use caution in:

  * Elderly
  * CKD (generally safer than glyburide)

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===== Repaglinide vs Sulfonylureas =====

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

  * Longer duration
  * Higher risk of prolonged hypoglycemia

Repaglinide:

  * Short-acting
  * Meal-based dosing
  * Lower prolonged hypoglycemia risk
  * More flexible for irregular eating patterns

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===== Repaglinide vs Other Diabetes Agents =====

Compared to:

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

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

  * Rapid-acting insulin secretagogue
  * Take before meals
  * Skip if meal skipped
  * Lower prolonged hypoglycemia risk than sulfonylureas
  * Significant CYP interactions (avoid with gemfibrozil)

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===== Related =====

  * [[endocrine:meglitinides:start|Meglitinides]]
  * [[endocrine:meglitinides:nateglinide|Nateglinide]]
  * [[endocrine:sulfonylureas:start|Sulfonylureas]]
  * [[endocrine:biguanides:metformin|Metformin]]