What is the dosing regimen for meglitinides (e.g. repaglinide, nateglinide) in the management of type 2 diabetes?

Meglitinide Dosing Regimen for Type 2 Diabetes Management

Repaglinide and nateglinide should be administered preprandially (within 30 minutes before meals) with a flexible meal-related dosing schedule, with repaglinide being the preferred meglitinide due to its superior glycemic efficacy.

Repaglinide Dosing

Initial Dosing

• Starting dose:
  • For patients with HbA1c <8%: 0.5 mg before each meal 1
  • For patients with HbA1c ≥8%: 1-2 mg before each meal 1

Dose Titration

• Dose may be doubled up to 4 mg per meal until satisfactory glycemic control is achieved 1
• Allow at least one week between dose adjustments to assess response 1
• Recommended dose range: 0.5-4 mg before meals 1
• Maximum daily dose: 16 mg 1

Administration Schedule

• Take within 30 minutes before meals 1
• May be dosed 2-4 times daily depending on meal pattern 1, 2
• Follow "one meal, one dose; no meal, no dose" principle 2
• Skip dose when skipping meals to reduce hypoglycemia risk 1

Special Populations

• Severe renal impairment (CrCl 20-40 mL/min):
  • Start with 0.5 mg before each meal 1
  • Gradually titrate as needed 1
• Drug interactions:
  • With cyclosporine: Do not exceed 6 mg total daily dose 1
  • With clopidogrel: Start at 0.5 mg before meals; do not exceed 4 mg total daily dose 1
  • Avoid concomitant use with gemfibrozil (contraindicated) 1

Nateglinide Dosing

Standard Dosing

• Less effective than repaglinide in lowering HbA1c 3
• Typical dose: 60-120 mg three times daily before meals 4, 5
• Take 10 minutes before meals 5

Clinical Considerations

Indications for Meglitinide Use

• Patients with erratic meal schedules 3
• Patients experiencing late postprandial hypoglycemia with sulfonylurea therapy 3
• Patients requiring flexible meal timing 6, 2
• Elderly patients or those with renal impairment (particularly repaglinide) 7

Efficacy

• Monotherapy HbA1c reduction: 0.5-1.5% with repaglinide; 0.5-0.8% with nateglinide 3
• Repaglinide is more effective than nateglinide in lowering HbA1c 3
• Particularly effective for controlling postprandial hyperglycemia 7

Monitoring and Adjustments

• Assess glycemic response after each dose adjustment
• Monitor for hypoglycemia, especially when combined with other glucose-lowering agents
• When initiating insulin therapy, reassess and potentially reduce meglitinide dose to minimize hypoglycemia risk 3

Safety Considerations

• Risk of hypoglycemia is less than with sulfonylureas but still present 3, 7
• Weight gain similar to sulfonylureas may occur 3
• Use with caution in patients with decreased kidney function due to increased risk of hypoglycemia 3
• Nateglinide has increased active metabolites with decreased kidney function, while repaglinide does not 3

Practical Application

• Meglitinides are particularly useful as an alternative to sulfonylureas for patients who:
  • Have irregular eating patterns
  • Need flexible dosing around meals
  • Experience hypoglycemia with sulfonylureas
  • Have renal impairment (especially repaglinide)
• The rapid onset and short duration of action allow for flexible meal schedules without compromising glycemic control 2