Repaglinide

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

It is taken before meals and primarily targets postprandial hyperglycemia.

→ Meglitinides

Repaglinide 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

Important:

• Rapid onset
• Short duration
• Insulin secretion is NOT glucose-dependent
• Lower risk of prolonged hypoglycemia than sulfonylureas

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

Requires functioning beta cells.

• Taken before each meal
• Skip dose if meal is skipped
• Flexible for irregular meal schedules

• Rapid absorption
• Short half-life
• Hepatic metabolism (CYP3A4 and CYP2C8)

Drug interactions are clinically relevant.

CYP3A4 inhibitors may increase repaglinide levels.

Important interaction:

• Gemfibrozil (CYP2C8 inhibitor) → significantly increases repaglinide concentration
• Combination is generally avoided

Common:

• Hypoglycemia (less severe than sulfonylureas)
• Weight gain

Lower prolonged hypoglycemia risk compared to:

• Sulfonylureas

• Type 1 Diabetes
• Severe hepatic impairment

Use caution in:

• Elderly
• CKD (generally safer than glyburide)

Sulfonylureas:

• Longer duration
• Higher risk of prolonged hypoglycemia

Repaglinide:

• Short-acting
• Meal-based dosing
• Lower prolonged hypoglycemia risk
• More flexible for irregular eating patterns

Compared to:

• Metformin → more hypoglycemia
• GLP-1 Receptor Agonists → no weight loss
• SGLT2 Inhibitors → no heart failure benefit

• Rapid-acting insulin secretagogue
• Take before meals
• Skip if meal skipped
• Lower prolonged hypoglycemia risk than sulfonylureas
• Significant CYP interactions (avoid with gemfibrozil)

• Meglitinides
• Nateglinide
• Sulfonylureas
• Metformin