Usage
- Nateglinide is prescribed for type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycemic control in adults. It is specifically used to address postprandial hyperglycemia (elevated blood sugar after meals).
- Pharmacological Classification: Meglitinide, a short-acting insulin secretagogue.
- Mechanism of Action: Nateglinide stimulates insulin release from the pancreas by binding to and closing ATP-sensitive potassium channels on the pancreatic beta-cell membrane, leading to membrane depolarization and opening of voltage-dependent calcium channels. The influx of calcium triggers insulin secretion.
Alternate Names
- International Nonproprietary Name (INN): Nateglinide
- Brand Names: Starlix is a popular brand name.
How It Works
- Pharmacodynamics: Nateglinide rapidly increases insulin secretion, starting within 20 minutes of oral administration and peaking around 1 hour post-dose. The effect on insulin levels returns to baseline by 4 hours. This short duration of action makes it specifically effective in controlling postprandial glucose excursions.
- Pharmacokinetics: Nateglinide is rapidly absorbed after oral administration. It is primarily metabolized by CYP2C9 and CYP3A4 enzymes in the liver, and its metabolites are primarily excreted in the urine with a small amount excreted in the feces. The elimination half-life is approximately 1.5 hours.
- Mode of Action: Nateglinide binds to a distinct site on the pancreatic beta-cell ATP-sensitive potassium channel, different from the sulfonylurea binding site. This binding blocks the channel, leading to depolarization and ultimately, insulin secretion.
- Elimination Pathways: Predominantly hepatic metabolism via CYP2C9 and CYP3A4, followed by renal excretion of metabolites.
Dosage
Standard Dosage
Adults:
- Initial: 120 mg three times daily before meals (within 1-30 minutes).
- Alternatively: 60 mg three times daily before meals for patients near their glycemic target (HbA1c) when starting treatment.
- Maximum: Information on maximum dosage not available through provided sources.
- Frequency: Three times daily before main meals.
- If a meal is skipped, the corresponding dose should also be skipped to prevent hypoglycemia.
Children:
- The safety and effectiveness of nateglinide in pediatric patients have not been established.
Special Cases:
- Elderly Patients: No specific dose adjustment is required, but monitor for increased sensitivity to hypoglycemia.
- Patients with Renal Impairment: No dose adjustment is necessary for mild to severe renal impairment.
- Patients with Hepatic Dysfunction: No dose adjustment is needed for mild hepatic impairment. Use with caution in moderate to severe hepatic impairment.
- Patients with Comorbid Conditions: No specific dosage adjustments described for comorbid conditions through these sources. Consider individual patient factors and closely monitor.
Clinical Use Cases
- The provided sources do not contain specific dosage recommendations for clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.
Dosage Adjustments
- Dose adjustments should be based on periodic HbA1c measurements and individual patient response.
Side Effects
Common Side Effects
- Upper respiratory tract infection
- Back pain
- Flu-like symptoms
- Dizziness
- Joint pain or inflammation
- Diarrhea
- Bronchitis
- Cough
- Weight gain
- Hypoglycemia (sweating, trembling, dizziness, increased appetite, palpitations, nausea, fatigue, weakness)
Rare but Serious Side Effects
- Severe allergic reactions (hives, difficulty breathing, swelling of face, lips, tongue, or throat)
- Severe hypoglycemia
- Jaundice
- Hepatitis
Long-Term Effects
- Potential long-term effects are not extensively detailed in the provided sources.
Adverse Drug Reactions (ADR)
- Severe hypoglycemia requiring urgent medical attention.
- Allergic reactions.
Contraindications
- Hypersensitivity to nateglinide or its components.
- Type 1 diabetes mellitus.
- Diabetic ketoacidosis.
- Severe hepatic impairment.
Drug Interactions
- CYP450 Interactions: Nateglinide is metabolized by CYP2C9 and CYP3A4. Drugs that inhibit or induce these enzymes can affect nateglinide levels.
- Other Interactions: Numerous drug interactions are possible. Consult a comprehensive drug interaction resource for a complete list before prescribing.
- Examples: Baricitinib, efavirenz, ethanol, ivosidenib, gemfibrozil, and many others.
- Food and Lifestyle: Alcohol can increase the risk of hypoglycemia. Skipping meals can also lead to hypoglycemia.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: Category C. Nateglinide should not be used during pregnancy unless the potential benefit outweighs the risk to the fetus.
- Breastfeeding: It is unknown if nateglinide passes into breast milk. It is recommended to avoid nateglinide during breastfeeding or consider an alternative therapy.
Drug Profile Summary
- Mechanism of Action: Stimulates insulin secretion by binding to and closing ATP-sensitive potassium channels on pancreatic beta-cells.
- Side Effects: Hypoglycemia, upper respiratory infections, back pain, flu-like symptoms, dizziness, joint pain.
- Contraindications: Type 1 diabetes, diabetic ketoacidosis, severe hepatic impairment, hypersensitivity.
- Drug Interactions: Numerous; consult a comprehensive drug interaction resource.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: 120 mg or 60 mg three times daily before meals.
- Monitoring Parameters: Blood glucose, HbA1c, liver function tests if indicated.
Popular Combinations
- Metformin: Commonly used in combination with metformin to enhance glycemic control.
Precautions
- General Precautions: Monitor for hypoglycemia, especially in elderly, malnourished, and renally impaired patients. Assess adherence to diet and medication regimen.
- Specific Populations: See Dosage section.
- Lifestyle Considerations: Counsel patients on the importance of regular meals, moderate alcohol consumption, and appropriate management of exercise to prevent hypoglycemia.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Nateglinide?
A: The recommended starting dose is 120 mg three times daily before meals. Patients near their HbA1c goal can start with 60 mg three times daily before meals.
Q2: How does Nateglinide differ from sulfonylureas?
A: Nateglinide has a shorter duration of action and a different binding site on the beta-cell ATP-sensitive potassium channel, leading to a more targeted effect on postprandial glucose and a potentially lower risk of hypoglycemia.
Q3: Can Nateglinide be used in patients with renal impairment?
A: Yes, no dose adjustment is necessary for patients with mild to severe renal impairment.
Q4: What are the most common side effects of Nateglinide?
A: Hypoglycemia, upper respiratory infections, back pain, flu-like symptoms, dizziness, and joint pain.
Q5: Is Nateglinide safe to use during pregnancy?
A: No, Nateglinide is a pregnancy category C drug and should be avoided during pregnancy unless the benefits outweigh the risks.
Q6: What should patients do if they skip a meal?
A: Patients should skip their scheduled dose of Nateglinide if they skip a meal to avoid hypoglycemia.
Q7: Can Nateglinide be used with other diabetes medications?
A: Yes, nateglinide can be used in combination with metformin, thiazolidinediones. However, it is not recommended to use it together with sulfonylureas due to the increased risk of hypoglycemia.
Q8: How should Nateglinide be administered?
A: Nateglinide should be taken orally 1 to 30 minutes before main meals (usually breakfast, lunch, and dinner).
Q9: How does Nateglinide work at the cellular level?
A: Nateglinide binds to a specific site on the ATP-sensitive potassium channels in pancreatic beta-cells. This binding inhibits the channel’s activity, causing membrane depolarization and subsequent opening of voltage-gated calcium channels. The resulting influx of calcium triggers the release of insulin.
Q10: What are the contraindications to using Nateglinide?
A: Nateglinide is contraindicated in patients with type 1 diabetes mellitus, diabetic ketoacidosis, hypersensitivity to nateglinide, and severe hepatic impairment.
