Repaglinide

• Type 2 Diabetes
• Postprandial Hyperglycemia
• Glycemic Control

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

Mechanism of Action

Repaglinide stimulates insulin secretion from pancreatic beta cells:

• Closes ATP-sensitive potassium channels: Binds to SUR1 subunit (different binding site than sulfonylureas)
• Depolarizes beta cell membrane: Opens voltage-dependent calcium channels
• Increases intracellular calcium: Triggers insulin granule exocytosis
• Rapid onset, short duration: Mimics physiological meal-time insulin response

The glucose-dependent action and short half-life result in lower hypoglycemia risk compared to sulfonylureas.

Available Formulations

Repaglinide is available as oral tablets:

• 0.5 mg tablets
• 1 mg tablets
• 2 mg tablets

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

Dosing Guidelines

For Patients Not Previously Treated or with HbA1c <8%:

• Starting dose: 0.5 mg before each meal

For Patients Previously Treated or with HbA1c ≥8%:

• Starting dose: 1 mg or 2 mg before each meal

Titration:

• May double preprandial dose weekly up to 4 mg before each meal
• Maximum single dose: 4 mg
• Maximum daily dose: 16 mg

Timing:

• Take within 15 minutes before meals (up to 30 minutes before)
• Skip dose if skipping a meal
• Add dose if adding a meal

Important Safety Information

Contraindications:

• Diabetic ketoacidosis
• Type 1 diabetes
• Concomitant use with gemfibrozil
• Known hypersensitivity to repaglinide

Warnings and Precautions:

• Hypoglycemia: Risk increases with skipped meals, alcohol, renal/hepatic impairment, or combination therapy
• Cardiovascular safety: Contains a cardiovascular outcomes study requirement
• Hepatic impairment: Use with caution; longer exposure expected
• Drug interactions: Many drugs affect repaglinide levels through CYP2C8 and CYP3A4

Gemfibrozil Interaction: Gemfibrozil dramatically increases repaglinide levels (8-fold) and is contraindicated.

Drug Interactions

CYP2C8 Inhibitors:

• Gemfibrozil: Contraindicated (8-fold increase in repaglinide AUC)
• Clopidogrel: May increase repaglinide exposure; consider dose reduction
• Trimethoprim, deferasirox: May increase levels

CYP3A4 Inhibitors:

• Itraconazole, ketoconazole, erythromycin may increase repaglinide levels

CYP2C8/3A4 Inducers:

• Rifampin: Reduces repaglinide levels by 80%; may need dose increase

Other:

• Beta-blockers: May mask hypoglycemia symptoms
• NPH insulin: Can be used in combination, but not FDA-approved

Special Populations

• Hepatic Impairment: Use with caution; consider longer dosing intervals
• Renal Impairment: Start with 0.5 mg; titrate carefully (reduced clearance)
• Elderly: Start conservatively; may be more susceptible to hypoglycemia
• Pregnancy: Not recommended; insulin preferred
• Pediatric: Safety and efficacy not established