Nateglinide
Other glucose-lowering drugs
Other glucose-lowering drugs
A fast, short-acting insulin secretagogue (glinide) taken just before meals to limit the glucose rise after eating in type 2 diabetes.
Quick facts
- Group
- Other glucose-lowering drugs
- Target
- ATP-sensitive potassium (KATP) channel of the beta cell, SUR1 subunit
- Used for
- Type 2 diabetes
- Key effects
- Hypoglycaemia · Upper respiratory symptoms · Dizziness
- Monitor
- Blood glucose · HbA1c · Hypoglycaemia episodes
- ATC
- A10BX03
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows repaglinide, another glinide, bound to SUR1 of the pancreatic KATP channel (hamster SUR1 with rat Kir6.2); nateglinide closes the same channel.
Nateglinide, a D-phenylalanine derivative, binds the KATP channel of pancreatic beta cells and closes it. The cell depolarizes, voltage-gated calcium channels open and insulin is released. Its onset is fast and its action brief, so it mainly lowers the glucose rise after meals. Its effect needs functioning beta cells.
- Binds the KATP channel (SUR1) of the beta cell
- Channel closes; the cell depolarizes
- Calcium enters and insulin granules are released
- A brief insulin burst limits the post-meal glucose rise
Indications
- Type 2 diabetes, with diet and exercise, alone or with metformin, to lower post-meal glucose Type 2 diabetes mellitus →
Adverse effects
Common
- Hypoglycaemia (the main adverse effect)
- Upper respiratory symptoms, cough, flu-like symptoms
- Joint aches, back pain
- Dizziness, diarrhoea
Contraindications
- Hypersensitivity to nateglinide
Key interactions
- CYP2C9 inhibitors (amiodarone, fluconazole, voriconazole), NSAIDs, salicylates, MAO inhibitors, non-selective beta-blockers
- Increase the glucose-lowering effect and hypoglycaemia risk.
- Thiazides, corticosteroids, thyroid hormone, sympathomimetics, CYP inducers (rifampicin, phenytoin, St John's wort)
- Reduce its effect; glucose may rise.
- Beta-blockers, clonidine, reserpine
- May mask the warning signs of hypoglycaemia.
What is monitored
- Blood glucose, including after meals
- HbA1c
- Hypoglycaemia episodes
Administration and safety
- Oral tablet, taken shortly before each main meal (within half an hour).
- If a meal is skipped, that dose is skipped.
- Not combined with sulfonylureas (same mechanism).
Pregnancy and breastfeeding
Data in pregnancy are limited; insulin is the usual treatment for diabetes in pregnancy.
Nursing care
- Before each dose: confirm the patient is about to eat.
- Teach hypoglycaemia recognition and treatment.
- Teach to skip the dose with a skipped meal.
- Review new medicines for interactions (azole antifungals, amiodarone, NSAIDs).
Pharmacokinetics
- Absorption
- Oral; absorbed within minutes and acts quickly.
- Metabolism
- Liver, mainly CYP2C9 and to a lesser extent CYP3A4.
- Elimination
- Rapid and complete elimination of drug and metabolites.
- Half-life
- Short, around an hour or two (label, Katzung).
Test yourself
Think of the answer, then tap the question to see it.
How does nateglinide release insulin?
It closes the beta-cell KATP channel, depolarizing the cell so calcium enters and insulin is released.
What should a patient on nateglinide do if a meal is skipped?
Skip that dose, to avoid hypoglycaemia.
Which liver enzyme mainly metabolizes nateglinide?
CYP2C9 (and to a lesser extent CYP3A4).
Connections
← 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: Nateglinide: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - NATEGLINIDE tablet (DailyMed (U.S. National Library of Medicine), 2025); Cryo-EM structure of the pancreatic beta-cell SUR1 bound to ATP and repaglinide (RCSB Protein Data Bank, 2019).
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Representative model, for educational purposes only.