Repaglinide (Prandin) is a meglitinide taken before each meal to control post-meal glucose in type 2 diabetes. It lowers A1C by 1.0 to 1.5 percent and is metabolized in the liver, making it safer than sulfonylureas in mild to moderate kidney disease. Gemfibrozil is an absolute contraindication. Side effects include hypoglycemia, weight gain, and upper respiratory infection.
What Repaglinide Is
Repaglinide is a benzoic acid derivative classified as a meglitinide — a non-sulfonylurea insulin secretagogue. It was FDA approved as Prandin in December 1997 and is now available as a generic. Novo Nordisk markets the brand name. Repaglinide is taken before meals to stimulate brief insulin release that matches the post-meal glucose rise.
Who Qualifies
Repaglinide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. It is typically considered when:
- Post-meal hyperglycemia drives A1C elevation
- Meal patterns are irregular and a fixed-schedule sulfonylurea would cause hypoglycemia between meals
- Mild to moderate CKD (eGFR 30 to 60 mL/min) makes sulfonylureas high-risk
- Sulfa allergy precludes sulfonylureas (though true cross-reactivity is uncommon)
- Newer agents (DPP-4i, SGLT2i, GLP-1 RA) are not available, tolerated, or affordable
How It Works
Repaglinide binds the SUR1 component of the ATP-sensitive potassium channel on pancreatic beta cells — a different binding site from sulfonylureas but the same channel target. Channel closure depolarizes the cell, opens voltage-gated calcium channels, and triggers insulin granule release.
Onset of insulin release: 15 to 30 minutes. Peak: 1 hour. Duration: 4 to 6 hours. The effect requires functional beta cells and the presence of glucose — repaglinide’s insulinotropic effect is glucose-dependent, so it is less likely to cause hypoglycemia than long-acting sulfonylureas at very low glucose levels.
Dosing
| Situation | Starting Dose | Maximum Single Dose | Maximum Daily Dose |
|---|---|---|---|
| A1C <8% or treatment-naive | 0.5 mg before each meal | 4 mg | 16 mg |
| A1C ≥8% or prior diabetes treatment | 1-2 mg before each meal | 4 mg | 16 mg |
| Severe renal impairment (eGFR <30) | 0.5 mg before each meal | Titrate carefully | — |
| Hepatic impairment | 0.5 mg with longer intervals between titrations | — | — |
Repaglinide is taken 15 to 30 minutes before each meal. Dose can be adjusted weekly based on glucose response. If a meal is skipped, the dose is skipped; if an extra meal is added, an extra dose can be taken.
Expected Effect on A1C and Glucose
- Average A1C reduction: 1.0 to 1.5 percent
- 2-hour post-meal glucose reduction: 50 to 90 mg/dL
- Fasting glucose reduction: 30 to 50 mg/dL
- Weight effect: +1 to 3 kg
Repaglinide produces somewhat more weight gain and more hypoglycemia than nateglinide because of its greater potency and slightly longer duration of action. Combined with metformin, A1C reductions can reach 1.5 to 2.0 percent.
Common Side Effects
- Hypoglycemia — more common than with nateglinide; usually mild
- Upper respiratory infection — 16%
- Headache — 11%
- Sinusitis — 6%
- Arthralgia — 6%
- Diarrhea — 5%
- Constipation — 3%
- Weight gain — modest
Drug Interactions
| Drug | Effect | Management |
|---|---|---|
| Gemfibrozil | ~10-fold rise in repaglinide levels; prolonged hypoglycemia | Contraindicated |
| Clopidogrel | Significant rise in repaglinide levels via CYP2C8 inhibition | Avoid or reduce dose; monitor |
| Itraconazole, ketoconazole | CYP3A4 inhibition raises repaglinide levels | Reduce dose; monitor |
| Cyclosporine | Higher levels via CYP3A4 and OATP1B1 | Use lowest effective dose |
| Rifampin, phenytoin, carbamazepine | CYP induction lowers repaglinide levels | May need higher dose |
| Beta-blockers | Mask hypoglycemia symptoms | Counsel patient on alternative signs |
| NSAIDs, salicylates, MAOIs | Enhance hypoglycemic effect | Monitor |
Serious Risks
- Hypoglycemia — more likely when meals are skipped, exercise is unusual, or interacting drugs are added
- Hypersensitivity reactions — rare; rash, urticaria
- Cardiovascular events — the FDA label notes a meta-analysis suggesting a non-significant trend for cardiovascular events; no dedicated CV outcome trial
Contraindications
- Type 1 diabetes
- Diabetic ketoacidosis
- Concomitant use of gemfibrozil
- Known hypersensitivity to repaglinide
Repaglinide vs Nateglinide vs Glipizide
| Feature | Repaglinide | Nateglinide | Glipizide |
|---|---|---|---|
| Class | Meglitinide | Meglitinide | Sulfonylurea |
| Onset | 15-30 min | 15 min | 30-60 min |
| Duration | 4-6 hr | 4 hr | 10-16 hr (IR), 24 hr (XL) |
| A1C reduction | 1.0-1.5% | 0.5-1.0% | 1.0-2.0% |
| Hypoglycemia risk | Moderate | Low-Moderate | High |
| Weight gain | +1-3 kg | +1-2 kg | +2-3 kg |
| Dosing | Before each meal | Before each meal | Once or twice daily |
| Renal safety | Good (hepatic clearance) | OK | Caution in CKD |
| Major interaction | Gemfibrozil contraindicated | Few | Several CYP2C9 |
| Cost | Generic, moderate | Generic, low | Generic, very low |
Where Repaglinide Fits Today
The ADA 2024 Standards of Care prefer metformin, GLP-1 RAs, SGLT2 inhibitors, and other newer agents over meglitinides for most patients. Repaglinide retains specific niches:
- Mild to moderate CKD where sulfonylurea hypoglycemia is amplified
- Irregular meal patterns where fixed-schedule dosing causes hypoglycemia
- Sulfa allergy patients
- Insurance limitations on newer brand-name agents
- Need for prandial coverage without injection (alternative to mealtime insulin)
Practical Considerations
- Take 15 to 30 minutes before each meal.
- If you skip the meal, skip the dose; if you add a meal, add a dose.
- Carry glucose source for hypoglycemia.
- Review medication list for gemfibrozil, clopidogrel, and CYP3A4 inhibitors before starting.
- Check post-meal glucose to assess effect.
- Generic repaglinide is available; brand-name Prandin is more expensive.
Related Reading
For more on this class, see our pieces on nateglinide and the meglitinides drug class. Also see our pillar on treatment options and our explanation of A1C levels.
The Bottom Line
Repaglinide (Prandin) is a meglitinide insulin secretagogue taken 15 to 30 minutes before each meal in type 2 diabetes. It produces 1.0 to 1.5 percent A1C reduction — more than nateglinide, similar to many sulfonylureas — with shorter-duration insulin release. Hepatic metabolism makes it usable in mild to moderate CKD where sulfonylureas would be risky. Gemfibrozil is an absolute contraindication. Common side effects include hypoglycemia, weight gain, and upper respiratory infection. Repaglinide today is a niche agent, mostly used for irregular eaters, CKD, or sulfa-allergic patients. Talk to your doctor about whether repaglinide fits your eating pattern, kidney function, and overall plan.
