====== Meglitinides ======

Meglitinides are short-acting insulin secretagogues used to control postprandial hyperglycemia.

They stimulate insulin release from pancreatic beta cells.

They have a lower risk of prolonged hypoglycemia compared to sulfonylureas.

→ [[endocrine:diabetes:start|Diabetes Pharmacology]]

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

Meglitinides bind 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

Key difference from sulfonylureas:

  * Very rapid onset
  * Short duration of action
  * Primarily affect postprandial glucose

Insulin secretion is NOT glucose-dependent, but shorter action reduces prolonged hypoglycemia risk.

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===== Agents =====

  * [[endocrine:meglitinides:repaglinide|Repaglinide]]
  * [[endocrine:meglitinides:nateglinide|Nateglinide]]

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

  * Modest HbA1c reduction
  * Strong postprandial glucose lowering
  * Weight gain (less than sulfonylureas)
  * Lower risk of prolonged hypoglycemia

Taken before meals.

If a meal is skipped, the dose should be skipped.

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===== Pharmacokinetic Features =====

  * Rapid absorption
  * Short half-life
  * Short duration of insulin stimulation

Repaglinide is more potent than nateglinide.

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

Common:

  * Hypoglycemia (less severe than sulfonylureas)
  * Weight gain

Lower risk of prolonged hypoglycemia compared to:

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

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

  * Type 1 Diabetes
  * Use caution in hepatic impairment

Repaglinide interacts with CYP3A4 inhibitors.

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===== Meglitinides vs Sulfonylureas =====

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

  * Longer duration
  * Higher hypoglycemia risk
  * Once or twice daily dosing

Meglitinides:

  * Short-acting
  * Meal-based dosing
  * Lower prolonged hypoglycemia risk
  * Target postprandial spikes

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===== Meglitinides vs Other Agents =====

Compared to:

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

Meglitinides are useful in patients with irregular meal patterns.

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

  * Close KATP channels like sulfonylureas
  * Short-acting
  * Take before meals
  * Skip dose if meal skipped
  * Lower prolonged hypoglycemia risk
  * Target postprandial glucose

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===== Related =====

  * [[endocrine:diabetes:start|Diabetes Pharmacology]]
  * [[endocrine:sulfonylureas:start|Sulfonylureas]]
  * [[endocrine:biguanides:metformin|Metformin]]
  * [[endocrine:glp1:start|GLP-1 Receptor Agonists]]