What is repaglinide?

Repaglinide: A Prandial Glucose Regulator

Repaglinide is a meglitinide class oral antidiabetic medication that stimulates insulin secretion from pancreatic beta cells to control blood glucose levels, particularly targeting postprandial glucose excursions in patients with type 2 diabetes mellitus. 1, 2

Mechanism of Action and Classification

Repaglinide belongs to the glinide class of medications, specifically the meglitinides. Unlike sulfonylureas, repaglinide:

• Binds to a different site on the sulfonylurea receptor on pancreatic beta cells 3
• Has a rapid onset and short duration of action 2
• Stimulates insulin secretion in a glucose-dependent manner 3
• Is chemically unrelated to sulfonylureas, being a carbamoylmethyl benzoic acid derivative 1, 4

Clinical Efficacy

Repaglinide demonstrates significant glycemic efficacy:

• Reduces HbA1c by 0.5-1.5% when used as monotherapy 2, 3
• Is more effective than nateglinide (another meglitinide) in lowering HbA1c 2
• Provides similar overall glycemic control to sulfonylureas in clinical trials 4, 5
• May have superior effects on postprandial glucose control compared to some sulfonylureas 4

Dosing and Administration

Repaglinide has unique dosing characteristics:

• Administered preprandially (within 30 minutes before meals) 2
• Typical dosage ranges from 0.5 to 4 mg taken before meals 4
• Allows for flexible meal-related dosing due to its rapid onset and short duration 2, 6
• Can be used with 2-4 meals per day without loss of efficacy 4

Advantages and Clinical Applications

Key advantages of repaglinide include:

• Flexible meal scheduling due to its short duration of action 2, 6
• Particularly useful for patients with irregular eating patterns 2
• Can be used in patients with renal impairment (unlike some other antidiabetic agents) 3, 2
• Lower risk of severe hypoglycemia compared to some sulfonylureas 6, 7
• Weight neutral or associated with less weight gain than some other antidiabetic medications 5

Combination Therapy

Repaglinide shows additive effects when used with:

• Metformin 4, 7
• Thiazolidinediones (rosiglitazone, pioglitazone) 4, 6
• Bedtime insulin 4

Side Effects and Precautions

Common adverse effects include:

• Hypoglycemia (though less severe than with sulfonylureas) 2, 6
• Upper respiratory tract infections 4
• Headache 4
• Potential weight gain (though less than with some sulfonylureas) 5

Special Populations

Repaglinide may be particularly beneficial in:

• Elderly patients who need flexible dosing 2
• Patients with renal impairment (as it's primarily metabolized by the liver) 2, 8
• Patients who experience hypoglycemia with sulfonylureas 2
• Patients with irregular meal schedules 2, 6

FDA Indication

Repaglinide is FDA-approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is not indicated for treatment of type 1 diabetes mellitus or diabetic ketoacidosis. 1

Practical Considerations

• Repaglinide should be taken before meals, with dosing adjusted based on meal patterns
• Missing a meal means the corresponding dose should be skipped, reducing hypoglycemia risk
• Monitoring for hypoglycemia is still necessary, especially when initiating therapy
• Drug interactions should be monitored, particularly with CYP3A4 inhibitors or inducers 7