What is the proper dosage and management of Repaglinide for type 2 diabetes?

Repaglinide Dosage and Management for Type 2 Diabetes

Repaglinide should be initiated at 0.5 mg before each meal for patients with HbA1c <8% and 1-2 mg before each meal for patients with HbA1c ≥8%, with a maximum dose of 4 mg per meal and 16 mg daily, taken within 30 minutes before meals. 1

Initial Dosing and Titration

• Starting dose is determined by baseline HbA1c: 0.5 mg before meals if HbA1c <8%, or 1-2 mg before meals if HbA1c ≥8% 1
• Dose should be doubled gradually (up to 4 mg per meal) until satisfactory glycemic control is achieved, with at least one week between dose adjustments 1
• Maximum daily dose is 16 mg 1
• Administer within 30 minutes before meals 1

Flexible Meal Dosing

• Repaglinide can be dosed 2,3, or 4 times daily depending on the patient's meal pattern 1
• Follow the "one meal, one dose; no meal, no dose" principle - if a meal is skipped, the corresponding dose should be skipped to reduce hypoglycemia risk 1, 2
• This flexible dosing regimen allows patients to vary their meal patterns without compromising glycemic control 2

Special Populations

• For patients with severe renal impairment (CrCl 20-40 mL/min), start with 0.5 mg before each meal and titrate cautiously 3, 1
• When GFR is ≤30 mL/min/1.73 m², start with 0.5 mg with each meal and titrate upwards cautiously 3
• Unlike some sulfonylureas, repaglinide can be used in patients with renal insufficiency as it doesn't have active metabolites that accumulate 3

Drug Interactions

• Contraindicated with gemfibrozil due to significant increase in repaglinide exposure 1
• Avoid concomitant use with clopidogrel; if unavoidable, limit repaglinide to 0.5 mg per meal with a maximum daily dose of 4 mg 1
• Limit total daily dose to 6 mg when used with cyclosporine 1
• Dose adjustments may be needed with strong CYP3A4 or CYP2C8 inhibitors or inducers 1

Efficacy and Monitoring

• Repaglinide reduces HbA1c by 0.5-1.5% and is particularly effective at controlling postprandial glucose excursions 3
• In treatment-naïve patients, repaglinide has been shown to decrease HbA1c by up to 2.3% compared to placebo 4
• Monitor blood glucose regularly, especially during the first 3-4 weeks after initiation 3
• Assess efficacy by measuring both fasting and postprandial glucose levels, as well as HbA1c 4, 2

Hypoglycemia Management

• Risk of hypoglycemia is lower with repaglinide than with sulfonylureas, especially when meals are skipped 3, 5
• If hypoglycemia occurs, reduce the repaglinide dose 1
• When adding repaglinide to insulin or insulin secretagogues, consider reducing the dose of these agents to minimize hypoglycemia risk 3

Advantages Over Sulfonylureas

• Short duration of action (half-life <1 hour) allows for more physiologic insulin secretion pattern 5
• Lower risk of severe hypoglycemia compared to some sulfonylureas, especially when meals are skipped 3, 5
• Can be used during fasting periods like Ramadan with less hypoglycemia risk than glibenclamide 3

Common Side Effects

• Hypoglycemia (though less severe than with sulfonylureas) 1
• Upper respiratory infections 1
• Headache 1
• Arthralgia 1
• Gastrointestinal effects (nausea, diarrhea) 1

By following these dosing guidelines and monitoring protocols, repaglinide can provide effective glycemic control while offering flexibility in meal timing for patients with type 2 diabetes.