Nateglinide

• Type 2 Diabetes
• Postprandial Hyperglycemia
• Glycemic Control

Nateglinide is a rapid-acting insulin secretagogue (meglitinide class) used to improve glycemic control in adults with type 2 diabetes mellitus. By stimulating insulin release in response to meals, it specifically targets postprandial glucose excursions.

Mechanism of Action

Nateglinide stimulates insulin secretion from pancreatic beta cells:

• Binds to and closes ATP-sensitive potassium channels on beta cell membranes
• Causes depolarization of the cell membrane
• Opens voltage-dependent calcium channels
• Increased intracellular calcium triggers insulin exocytosis

The insulin secretion is glucose-dependent and more rapid but shorter-acting than sulfonylureas. This results in meal-time insulin release that mimics physiological patterns.

Available Formulations

Nateglinide is available as oral tablets:

• 60 mg tablets
• 120 mg tablets

Tablets should be taken 1-30 minutes before meals.

Medical Uses

FDA-Approved Indication:

• Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus

May be used as:

• Monotherapy
• In combination with metformin or thiazolidinediones

Not indicated for combination with sulfonylureas due to similar mechanisms.

Dosing Guidelines

Adults:

• Starting dose: 120 mg three times daily before meals
• Patients near HbA1c goal: May start with 60 mg three times daily
• Take 1-30 minutes before meals
• Skip dose if skipping a meal

Timing: The rapid onset and short duration are designed for preprandial (before meal) dosing. Do not take if meal is not consumed.

Important Safety Information

Contraindications:

• Type 1 diabetes mellitus
• Diabetic ketoacidosis
• Known hypersensitivity to nateglinide

Warnings and Precautions:

• Hypoglycemia: Risk increases with irregular meal patterns, strenuous exercise, alcohol, or combination with other antidiabetics
• Hepatic impairment: Use with caution
• Not a substitute for insulin in patients requiring insulin

Hypoglycemia Management: Patients should carry glucose tablets and know symptoms of hypoglycemia.

Drug Interactions

• CYP2C9 inhibitors (fluconazole, amiodarone): May increase nateglinide levels
• CYP2C9 inducers (rifampin): May decrease nateglinide levels
• Other antidiabetics: Additive hypoglycemic effect
• Beta-blockers: May mask hypoglycemia symptoms
• Corticosteroids, thyroid hormones: May reduce glucose-lowering effect
• NSAIDs, salicylates: May enhance glucose-lowering effect

Special Populations

• Hepatic Impairment: Use with caution in moderate to severe impairment
• Renal Impairment: No dose adjustment needed for mild to moderate; use with caution in severe impairment or dialysis
• Elderly: Start conservatively; may be more susceptible to hypoglycemia
• Pregnancy: Category C; not recommended; insulin preferred
• Pediatric: Safety and efficacy not established