Drug information of nateglinide


Drug group: blood sugar

nateglinide is used to lower blood sugar in patients with high blood sugar (diabetes).

Mechanism of effect

Nateglinide activity is dependent on the presence functioning β cells and glucose. In contrast to sulfonylurea insulin secretatogogues, nateglinide has no effect on insulin release in the absence of glucose. Rather, it potentiates the effect of extracellular glucose on ATP-sensitive potassium channel and has little effect on insulin levels between meals and overnight. As such, nateglinide is more effective at reducing postprandial blood glucose levels than fasting blood glucose levels and requires a longer duration of therapy (approximately one month) before decreases in fasting blood glucose are observed. The insulinotropic effects of nateglinide are highest at intermediate glucose levels (3 to 10 mmol/L) and it does not increase insulin release already stimulated by high glucose concentrations (greater than 15 mmol/L). Nateglinide appears to be selective for pancreatic β cells and does not appear to affect skeletal or cardiac muscle or thyroid tissue.


    Insulin secretion by pancreatic β cells is partly controlled by cellular membrane potential. Membrane potential is regulated through an inverse relationship between the activity of cell membrane ATP-sensitive potassium channels (ABCC8) and extracellular glucose concentrations. Extracellular glucose enters the cell via GLUT2 (SLC2A2) transporters. Once inside the cell, glucose is metabolized to produce ATP. High concentrations of ATP inhibit ATP-sensitive potassium channels causing membrane depolarization. When extracellular glucose concentrations are low, ATP-sensitive potassium channels open causing membrane repolarization. High glucose concentrations cause ATP-sensitive potassium channels to close resulting in membrane depolarization and opening of L-type calcium channels. The influx of calcium ions stimulates calcium-dependent exocytosis of insulin granules. Nateglinide increases insulin release by inhibiting ATP-sensitive potassium channels in a glucose-dependent manner.


absorption: Rapidly absorbed following oral administration prior to a meal, absolute bioavailability is estimated to be approximately 73%. Peak plasma concentrations generally occur within 1 hour of oral administration. Onset of action is <20 minutes and the duration of action is approximately 4 hours. 
volume of destribution: 10 liters in healthy subjects
protein binding: 98% bound to serum proteins, primarily serum albumin and to a lesser extent α1
acid glycoprotein
metabolism: Hepatic, via cytochrome P450 isoenzymes CYP2C9 (70%) and CYP3A4 (30%). Metabolism is via hydroxylation followed by glucuronidation. The major metabolites have less antidiabetic activity than nateglinide, but the isoprene minor metabolite has antidiabetic activity comparable to that of nateglinide.
Route of elimination: Urine (83%) and feces (10%)
half-life: 1.5 hours

Drug indications

diabetes mellitus type2


Type 2 DM Monotherapy, or With Metformin
120 mg PO q8hr; 60 mg PO q8hr if patient near goal HbA1C
Take dose 1-30 minutes before meal

Drug contraindications

allergic reaction


Patients with risk of severe hypoglycemia: elderly, malnourished, adrenal or pituitary insufficiency, hepatic insufficiency
Patients with stress due to infection, fever, trauma, or surgery
Not to be used in combination with an insulin secretagogue (eg, glyburide)
Not to be used as substitute for metformin monnotherapy but as adjunctive

Pregnancy level

Group c - Not adequate studies in pregnant women

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

Breast feeding warning


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