Pharmacology · Other glucose-lowering drugs
Repaglinide !
A short-acting meglitinide taken just before meals: it gives a quick burst of insulin. Never combined with gemfibrozil.
Updated 2026-11-01
The figure shows repaglinide bound to SUR1 (hamster SUR1 with rat Kir6.2, very similar to the human proteins).
Mechanism of action
Repaglinide is a benzoic acid derivative, not a sulfonylurea, that binds SUR1 at a site that overlaps but differs from the sulfonylurea site and closes the KATP channel. The beta cell depolarizes and releases insulin. Onset is fast and the effect brief, so it covers the meal it is taken with.
- Binds SUR1 on the beta-cell KATP channel
- The channel closes and the membrane depolarizes
- Calcium channels open and insulin granules are released
- Glucose falls, even when it is already low
Pharmacokinetics
- Absorption
- Oral, quick absorption; taken shortly before each meal.
- Metabolism
- In the liver by CYP2C8 and CYP3A4.
- Elimination
- Mostly in bile and feces.
- Half-life
- Short, which explains the brief action.
Indications
- Type 2 diabetes, with diet and exercise, mainly to control glucose after meals Type 2 diabetes mellitus →
Adverse effects
Common
- Hypoglycemia
- Weight gain
- Upper respiratory infection, headache
Contraindications
- Use together with gemfibrozil
- Hypersensitivity to repaglinide
- Not for type 1 diabetes or ketoacidosis
Key interactions
- Gemfibrozil
- Contraindicated: blocks CYP2C8 and raises repaglinide levels sharply; severe hypoglycemia.
- Clopidogrel
- Raises repaglinide levels (CYP2C8); combination avoided.
- Cyclosporine and other CYP2C8 or CYP3A4 inhibitors
- Raise repaglinide levels; glucose is checked more often.
- Insulin, sulfonylureas
- Add to hypoglycemia.
What is monitored
- Capillary glucose, especially after meals
- HbA1c
Administration and safety
- Oral tablet shortly before each main meal.
- If a meal is skipped, that dose is skipped too.
- Check for gemfibrozil or clopidogrel on the medication list before giving it.
Nursing care
- Before: confirm the patient will eat.
- During: watch for hypoglycemia after meals.
- Teach: carry fast sugar and recognize hypoglycemia.
Pregnancy and breastfeeding
Limited data have not shown a clear risk; insulin is the usual choice in pregnancy.
Test yourself
Think of the answer, then tap the question to see it.
Why is repaglinide contraindicated with gemfibrozil?
Gemfibrozil inhibits CYP2C8, the main enzyme that clears repaglinide, causing very high levels and severe hypoglycemia.
What should a patient on repaglinide do about a skipped meal?
Skip that dose: the drug is meant to cover the meal it accompanies.
Is repaglinide a sulfonylurea?
No. It is a meglitinide (glinide) that closes the same KATP channel through a different binding site on SUR1.
Related drugs
Related conditions
← Back to the class: Other glucose-lowering drugs
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Repaglinide: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - REPAGLINIDE tablet (DailyMed (U.S. National Library of Medicine), 2026); Cryo-EM structure of the pancreatic beta-cell SUR1 bound to ATP and repaglinide (RCSB Protein Data Bank, 2019); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake
Representative model, for educational purposes only.