====== Nateglinide ======

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

It has a very rapid onset and short duration of action.

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

--------------------------------------------------------------------

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

Nateglinide 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

Key distinction:

  * Faster onset than repaglinide
  * Very short duration
  * Slightly more glucose-dependent insulin release

This results in lower risk of prolonged hypoglycemia compared to sulfonylureas.

--------------------------------------------------------------------

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

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

Requires functioning pancreatic beta cells.

--------------------------------------------------------------------

===== Dosing =====

  * Taken immediately before meals
  * Skip dose if meal skipped
  * Useful for irregular meal patterns

--------------------------------------------------------------------

===== Pharmacokinetics =====

  * Rapid absorption
  * Very short half-life
  * Hepatic metabolism (CYP2C9 and CYP3A4)

Shorter duration than:

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

--------------------------------------------------------------------

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

Common:

  * Hypoglycemia (generally mild)
  * Weight gain

Lower risk of prolonged hypoglycemia compared to:

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

--------------------------------------------------------------------

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

  * Type 1 Diabetes
  * Severe hepatic impairment

Use caution in:

  * Elderly
  * Renal impairment

--------------------------------------------------------------------

===== Nateglinide vs Repaglinide =====

[[endocrine:meglitinides:repaglinide|Repaglinide]]:

  * More potent
  * Slightly longer duration
  * Stronger HbA1c reduction

Nateglinide:

  * Very short-acting
  * Slightly lower hypoglycemia risk
  * Primarily targets postprandial glucose

--------------------------------------------------------------------

===== Nateglinide vs Sulfonylureas =====

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

  * Longer duration
  * Higher risk of prolonged hypoglycemia

Nateglinide:

  * Short-acting
  * Meal-based dosing
  * Lower prolonged hypoglycemia risk

--------------------------------------------------------------------

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

  * Rapid-acting insulin secretagogue
  * Take before meals
  * Skip dose if meal skipped
  * Shorter duration than repaglinide
  * Lower prolonged hypoglycemia risk than sulfonylureas

--------------------------------------------------------------------

===== Related =====

  * [[endocrine:meglitinides:start|Meglitinides]]
  * [[endocrine:meglitinides:repaglinide|Repaglinide]]
  * [[endocrine:sulfonylureas:start|Sulfonylureas]]
  * [[endocrine:biguanides:metformin|Metformin]]