Starlix (nateglinide)

Nateglinide, a meglitinide derivative (glinide), is a short-acting, insulinotropic antidiabetic agent.

Nateglinide, a d-phenylalanine derivative, is an insulinotropic antidiabetic agent. Like repaglinide, nateglinide is a meglitinide-derivative (glinide) antidiabetic agent that is structurally unrelated to oral sulfonylurea antidiabetic agents and repaglinide. Functioning pancreatic beta-cells are required for nateglinide's hypoglycemic activity since the drug lowers blood glucose concentrations principally by augmenting endogenous insulin secretion from the pancreas in response to a meal.

The extent of insulin release is glucose dependent and diminishes at low blood glucose levels. Nateglinide interacts with the ATP-sensitive potassium channel on pancreatic beta-cells; nateglinide is highly tissue selective with low affinity for heart and skeletal muscle.

Following oral administration of nateglinide immediately prior to a meal, peak plasma concentration occurs within 1 hour; the absolute bioavailability is 73%. Nateglinide stimulates pancreatic insulin secretion within 20 minutes of oral administration. The pharmacokinetics of nateglinide are not affected by the composition of a meal (e.g., high protein, fat, or carbohydrate); when given with or after meals, AUC is unaffected but there is a delay in the rate of absorption characterized by a decrease in peak plasma concentrations and a delay in time to peak plasma concentration.

Peak plasma levels are significantly reduced when nateglinide is administered 10 minutes prior to a liquid meal as compared to a solid meal. Nateglinide is extensively (98%) bound to plasma proteins, primarily serum albumin and to alpha1-acid glycoprotein to a lesser extent. Nateglinide is extensively metabolized by cytochrome P-450 (CYP) 2C9 and, to a lesser extent, CYP3A4 isoenzymes.

The major metabolites are less potent antidiabetic agents than the parent drug with the exception of the isoprene minor metabolite, which possesses potency similar to that of the parent compound. Based on nateglinide's ability to inhibit the metabolism of tolbutamide in vitro, the drug may be an inhibitor of CYP2C9 in vivo. The average elimination half-life of nateglinide is 1.5 hours.

Nateglinide and its metabolites are rapidly and completely eliminated following oral administration; 83% of radiolabeled nateglinide was recovered in the urine (16% as parent drug) and 10% was eliminated in the feces. No pharmacokinetic data are available in patients with mild (creatinine clearance 60--89 mL/minute) renal impairment. Patients with moderate and severe (creatinine clearance 15--50 mL/minute) renal impairment not on dialysis display similar apparent clearance, AUC, and peak plasma concentrations.

Patients with renal failure requiring dialysis exhibit reduced overall drug exposure and reduced plasma protein binding. In patients with mild hepatic impairment, an increase in peak plasma concentration and AUC of 37% and 30%, respectively, were observed compared to healthy matched control subjects. There are no data on the pharmacokinetics of nateglinide in patients with moderate-to-severe hepatic impairment.

Age, race, and sex do not influence the pharmacokinetics of nateglinide.

USES: Nateglinide is used alone or with other medications to control high blood sugar along with a proper diet and exercise program. It is used in people with type 2 diabetes. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems.

Proper control of diabetes may also lessen your risk of a heart attack or stroke. It works by stimulating the body to produce more insulin. Insulin is a natural substance that allows the body to properly use sugar from the diet.

Generic name: nateglinide
Pronunciation: (nah-TEGG-lin-ide)

The following indications are listed for Starlix:

• Type 2 Diabetes Mellitus

Also known as: Adult Onset Diabetes, Adult Onset Diabetes Mellitus, Adult Onset Dm, Diabetes Mellitus Type 2, Diabetes Mellitus Type Ii, Ketosis-Resistant Diabetes Mellitus, Ketosis-Resistant Dm, Maturity Onset Diabetes, Maturity Onset Diabetes Mellitus, Non-Insulin Dependent Diabetes Mellitus, Non-Insulin-Dependent Diabetes Mellitus, Type Ii Diabetes Mellitus.

No ICD codes are available for this drug.