Should we add ripaglinide 0.5-1 mg before meals?

Repaglinide Dosing Recommendation

Yes, adding repaglinide 0.5 mg before meals (0-1-1 pattern) taken 15 minutes prior to food is appropriate, particularly if the patient has chronic kidney disease with eGFR <30 mL/min/1.73 m² or is at higher risk for hypoglycemia. 1, 2

Dosing Strategy Based on Renal Function

For patients with normal to mild-moderate renal impairment (eGFR >30):

• Standard dosing can begin at 0.5-2 mg before each meal 2
• No initial dose adjustment is required 1

For patients with severe renal impairment (eGFR <30 mL/min/1.73 m²):

• Must initiate conservatively at 0.5 mg with meals 1
• Titrate upwards cautiously based on glucose response 1
• This conservative approach is critical because repaglinide can accumulate when kidney function decreases 1

Timing Relative to Meals

Repaglinide can be administered flexibly:

• At the start of a meal, 15 minutes before, or 30 minutes before with equivalent blood glucose-lowering effect 2
• The 15-minute pre-meal timing you propose is well-supported and allows optimal prandial insulin secretion 2, 3

Meal-Pattern Flexibility

A key advantage of repaglinide is dose-to-meal matching:

• Dosing can be adjusted to 2,3, or 4 meals per day with maintained glycemic control 2, 3
• Your 0-1-1 pattern (skipping breakfast dose) is acceptable if the patient doesn't eat breakfast 2, 3
• If a meal is skipped, the corresponding repaglinide dose should be skipped to avoid hypoglycemia 3

Critical Safety Considerations

Hypoglycemia risk management:

• Repaglinide's rapid onset (t_max <1 hour) and short duration (t_1/2 <1 hour) reduce hypoglycemia risk compared to sulfonylureas 4, 5, 3
• When meals are missed, repaglinide shows significantly lower hypoglycemia rates than glibenclamide (0% vs 24% severe hypoglycemia) 3
• Overall hypoglycemia incidence is approximately 16% in long-term studies, similar to sulfonylureas, but severe hypoglycemia requiring hospitalization is reduced by 60% 5, 6

Hepatic metabolism advantage:

• Over 90% excreted via bile, making it safer in renal impairment than renally-cleared agents 4, 3
• Can be used even in patients with creatinine clearance 20-40 mL/min with careful titration 2

Titration Protocol

Start low and go slow:

• Begin at 0.5 mg before meals 1, 2
• Titrate weekly based on fasting and postprandial glucose monitoring 2
• Maximum dose is 4 mg per meal, but most patients achieve control at lower doses 2, 5
• In renal impairment, use longer intervals between dose adjustments 2

Common Pitfalls to Avoid

• Do not use fixed dosing without meal matching - this negates repaglinide's primary advantage and increases hypoglycemia risk 3
• Do not combine with gemfibrozil - this increases repaglinide exposure 2.3-fold 2
• Monitor closely in hepatic impairment - patients with chronic liver disease show 4-fold higher AUC 2
• Avoid in patients unable to maintain regular meal patterns unless they understand the skip-meal-skip-dose principle 3