Nateglinide is a short-acting oral anti-diabetic drug that belongs to the meglitinide class. It acts on the beta cells to stimulate insulin release. Another drug in the same class is repaglinide.

Nateglinide Uses:

• Diabetes mellitus, type 2:

  • Supplementing nutrition and exercise with treatment for persons with type 2 diabetes mellitus will improve and maximise glycemic control.

Nateglinide dose in Adults

Nateglinide dose in the treatment of Type 2 Diabetes mellitus:

• Initial and maintenance dose:
  • Before meals, take 120 mg three times day.
  • When starting medication, patients near to their intended HbA1C goal may be started on 60 mg three times per day.

Nateglinide dose in Children

Not recommended for use in children.

Pregnancy Risk Factor C

• Limited data are available on the effects of nateglinide in pregnancy outcomes.
• Poorly managed diabetes can lead to adverse maternal and fetal outcomes. This could include preeclampsia and preterm deliveries, preterm birth, complications and major birth defects.
• Preventing adverse outcomes by keeping maternal blood glucose and HbA1C as close as possible to the target levels, both before conception and during pregnancy. However, it is important to avoid significant low blood sugar.
• Other medications besides nateglinide should be taken into consideration for the treatment of diabetes mellitus during pregnancy.

Use of nateglinide during breastfeeding

• It is unknown if breast milk contains nateglinide.
• The manufacturer suggests that the mother decide whether to stop breastfeeding or discontinue using the drug because of the possibility of hypoglycemia. This decision should be taken in consideration of the mother's importance.

Nateglinide Dose in Kidney Disease:

• Mild to moderate impairment

  • There is no need to adjust the dosage.

• Severe impairment

  • Start conservatively with 60 mg three times daily, along with meals, if your eGFR is 30mL/minute/1.73m2.
  • Take care (especially if your eGFR is 15mL/minute/1.73m2) as there may be an accumulation of metabolites with hypoglycemic properties.

Nateglinide dose in Liver disease:

• Mild impairment (Child Puugh class A)

  • There is no need to adjust the dosage.

• Moderate to severe impairment (Child Puugh class B orC):

  • The manufacturer's labeling does not contain any dosage adjustments (hasn't been studied).
  • Use with caution because of the possibility for hypoglycemia.

Common Side Effects of Nateglinide:

• Respiratory:

  • Upper respiratory infection

Less Common Side Effects of Nateglinide:

• Central Nervous System:

  • Dizziness

• Endocrine & Metabolic:

  • Hypoglycemia
  • Increased Uric Acid
  • Weight Gain

• Neuromuscular & Skeletal:

  • Arthropathy

• Respiratory:

  • Flu-Like Symptoms

• Miscellaneous:

  • Accidental Injury

Contraindication to Nateglinide Include:

• Hypersensitivity to nateglinide and any component of the formulation

Warnings and precautions

• Hypoglycemia

  • Hypoglycemia may occur
  • Poor diet, changes in physical activity, the concurrent use of anti-antidiabetic medications, alcohol, renal impairment, and hepatic impairment are risk factors.
  • To avoid hypoglycemic episodes, it is important to choose the right patient, dose, and educate the patient.

• Pituitary or adrenal impairment

  • Patients who have pituitary and adrenal dysfunction should exercise caution since they may be more sensitive to the effects of glucose-lowering medications.

• Bariatric surgery

  • Absorption altered:

    • Gastric bypass and Sleeve Gastrectomy can cause changes in absorption.

  • Hypoglycemia:

    • Following gastric bypass, sleeve gastrectomy, and gastric band surgery, hypoglycemia may worsen (Mechanick 2013, 2013).
    • These methods may restore insulin secretion and sensitivity in part or in full (gastric bypass is the most effective, followed closely by the sleeve and then finally the band).
    • Hepatic insulin sensitivity and first-phase insulin secretion were dramatically enhanced in the days following gastric bypass or sleeve gastrectomy.
    • The effects of these operations could remain longer on peripheral insulin sensitivity. This could occur three to twelve months after surgery.
    • It is recommended to select antidiabetic drugs that are not hypoglycemic.

• Hepatic impairment

  • Patients with severe hepatic impairment (moderate-to-severe) should be cautious.

• Renal impairment

  • Patients with severe renal impairment should be cautious; prolonged hypoglycemia may occur due to the accumulation a metabolite that has hypoglycemic activities (Inoue 2003).

• Stress-related disorders:

  • If the patient is experiencing stress, such as fever, trauma, infection or surgery, it may be necessary for them to stop taking nateglinide.

Nateglinide: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Weighing
• Lipid profile
• Fasting blood glucose (periodically or during dosage titration)
• HbA1C: At least twice a year in patients who are complying with their treatment regimen and have stable glycemic control. Patients who are not achieving treatment goals or who have had therapy adjustments every three months.

How to administer Nateglinide?

• Oral: Take 1-30 minutes before you eat.
• If a meal has been skipped, the prescribed dose shouldn't need to be given in order to prevent hypoglycemia.

Mechanism of action of Nateglinide:

• It is a non-sulfonylurea hypoglycemic medication that depolarizes the membrane, inhibits ATP-dependent potassium channels, and makes calcium entry through calcium channels easier.
• Intracellular calcium stimulates the release of insulin by pancreatic beta cells.
• Nateglinide-induced Insulin Release is Glyce-dependent

The onset of action:

• Insulin secretion: ~20 minutes

Peak effect:

• 1 hour

Duration:

• 4 hours

Absorption:

• Rapid

Protein binding:

• 98%, primarily to albumin

Metabolism:

• Hepatic via hydroxylation followed by glucuronide conjugation via CYP2C9 (70%) and CYP3A4 (30%) to metabolites, including M1 (a major metabolite)

Bioavailability:

• 73%

Half-life elimination:

• 1.5 hours

Time to peak:

• ≤1 hour

Excretion:

• Urine (83%, 16% as unchanged drug);
• feces (10%)

International Brands of Nateglinide:

• Starlix
• Antangping
• Diabex
• Fastic
• Glinade
• Glinate
• Glunat
• Glytan
• Luoyu
• Nopik
• Novirep
• Starlidine

Nateglinide Brand Names in Pakistan: