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.

→ Meglitinides

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.

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

Requires functioning pancreatic beta cells.

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

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

Shorter duration than:

• Repaglinide

Common:

• Hypoglycemia (generally mild)
• Weight gain

Lower risk of prolonged hypoglycemia compared to:

• Sulfonylureas

• Type 1 Diabetes
• Severe hepatic impairment

Use caution in:

• Elderly
• Renal impairment

Repaglinide:

• More potent
• Slightly longer duration
• Stronger HbA1c reduction

Nateglinide:

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

Sulfonylureas:

• Longer duration
• Higher risk of prolonged hypoglycemia

Nateglinide:

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

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

• Meglitinides
• Repaglinide
• Sulfonylureas
• Metformin