Medication Classification and Mechanism
Nateglinide (Starlix) is an oral antidiabetic agent classified as a meglitinide or rapid-acting insulin secretagogue that stimulates insulin release promptly after pre-meal administration in a strongly glucose-dependent fashion 1
The drug works by binding to ATP potassium channels in pancreatic beta cells, resulting in increased beta-cell calcium influx that leads to rapid, short-lived insulin release 3
Its insulinotropic effects are short in duration, specifically targeting postprandial hyperglycemia with low potential for hypoglycemia or sustained hyperinsulinemia 1
Clinical Pharmacology
Nateglinide is rapidly and completely absorbed in the small intestine with an estimated bioavailability of 72% 3
The drug has a plasma half-life of 1.4 hours and is rapidly eliminated, with only 13-14% of the dose recovered as unchanged drug in urine 2
Administration 10 minutes before meals is associated with optimal absorption kinetics (12% increase in Cmax and 52% decrease in tmax compared to fasted state) 2
Dosing
The maximum effective dosage is 120 mg taken 10 minutes before meals three times daily 3
Dosage regimens ranging from 60 to 240 mg have been evaluated in clinical trials 3
Efficacy and Clinical Use
Nateglinide's efficacy in reducing HbA1c in monotherapy (120 mg before meals) is comparable to metformin, sulfonylureas, thiazolidinediones, or acarbose (-0.5 to -1.5%) 1
When combined with metformin (which primarily reduces fasting glucose), nateglinide's effects are additive 1
The drug is particularly appropriate for newly diagnosed treatment-naive patients, elderly patients at risk for hypoglycemia, patients with kidney failure or mild hepatic impairment, and patients failing metformin or thiazolidinedione monotherapy 1