Repaglinide (Prandin) for Mealtime Glucose Control — Weight & Metabolism
Short-acting meglitinide insulin secretagogue for flexible mealtime dosing, offering rapid glucose-dependent insulin release with lower hypoglycemia risk than sulfonylureas.
Overview
Repaglinide is a short-acting meglitinide (non-sulfonylurea) insulin secretagogue that stimulates rapid, meal-related insulin release by closing ATP-sensitive potassium channels on pancreatic beta-cells at a different binding site than sulfonylureas. Onset within 15-30 minutes, duration 3-4 hours - designed for flexible mealtime dosing. HbA1c reduction of 1.4-1.8% in longer trials, comparable to sulfonylureas. More effective than nateglinide (HbA1c -1.6% vs -1.0%). Combination with metformin reduces HbA1c by 1.4%. Lower hypoglycemia risk vs sulfonylureas due to shorter duration of action. Useful for patients with irregular meal schedules and in CKD (hepatic metabolism). PMID: 15072694.
Indications
- Type 2 diabetes mellitus with irregular meal schedules
- Postprandial hyperglycemia requiring mealtime insulin secretion
- Alternative to sulfonylureas when lower hypoglycemia risk is desired
- CKD patients needing insulin secretagogue (hepatic metabolism, no renal dose adjustment)
- Elderly patients with variable eating patterns
Mechanism of Action
T2DM is characterized by loss of rapid, first-phase insulin release in response to meals, leading to postprandial hyperglycemia
Dosing
| Compound | Dose | Frequency | Notes |
|---|---|---|---|
| Repaglinide (Prandin) | 0.5 mg | Before each meal (2-4 times daily) | Starting dose for HbA1c <8% or treatment-naive patients |
| Repaglinide (Prandin) | 1-2 mg | Before each meal (2-4 times daily) | Starting dose for patients switched from other oral agents |
| Repaglinide (Prandin) | 4 mg | Before each meal (max 16mg/day) | Maximum single meal dose; titrate weekly based on glucose response |
Evidence Grade
GRADE A
Safety & Contraindications
- Hypoglycemia risk lower than sulfonylureas but still present, especially if meal is skipped after dosing
- MUST be taken 15-30 minutes before meals; skip dose if skipping meal to avoid hypoglycemia
- Weight gain of 1-3kg expected (insulin secretagogue mechanism)
- Hepatic metabolism via CYP2C8 and CYP3A4: significant interaction with gemfibrozil (contraindicated), clopidogrel, trimethoprim
- Caution with hepatic impairment: longer drug exposure; use lower doses and longer titration intervals
- Not recommended in combination with sulfonylureas (same mechanism, additive hypoglycemia risk)