Skip Navigation

DRUG RECORD

 

NATEGLINIDE

OVERVIEW
Nateglinide

 

Introduction

Nateglinide is an oral hypoglycemic agent and amino acid derivative that stimulates insulin secretion from the pancreas and is used in the therapy of type 2 diabetes.  Nateglinide has been linked to rare instances of clinically apparent acute liver injury.

 

Background

Nateglinide (na teg' li nide) is an insulin secretagogue that is similar in action but different in structure from the sulfonylureas.  It is a derivative of phenylalanine and stimulates insulin secretion by blocking ATP sensitive potassium channels in pancreatic beta-cells, causing cell membrane depolarization which results in calcium influx and insulin secretion.  Nateglinide has been shown to reduce the postprandial increase in glucose in patients with type 2 diabetes and improve glycemic control.  Nateglinide was approved for use in the United States in 2000.  The current indications are for management of type 2 diabetes used in combination with diet and exercise, with or without other oral hypoglycemic agents.  Nateglinide is available generically and under the brand name Starlix in tablets of 60 and 120 mg.  The typical initial dose in adults is 120 mg three times daily before meals.  Side effects of nateglinide include diarrhea, nausea, gastrointestinal upset, hypoglycemia, dizziness and rash.

 

Hepatotoxicity

In several large clinical trials, serum aminotransferase elevations were no more common with nateglinide than with placebo.  The enzyme elevations that occurred were asymptomatic and resolved rapidly with stopping therapy.  Since its approval and with wide scale use, the FDA and the sponsor have received reports of clinically apparent liver injury attributed to nateglinide.  However, none of these cases has been published and the clinical features, time to onset, course and outcome of the injury have not been described.  Thus, nateglinide is likely to be a very rare cause of clinically apparent liver disease.

 

Mechanism of Injury

The mechanism of nateglinide induced liver injury is not known, but nateglinide is extensively metabolized by the liver via the P450 system (CYP 2C9 and 3A4), and liver injury may be the result of production of a toxic or immunoreactive intermediate.

 

Outcome and Management

There is no information on results of rechallenge on cross sensitivity to hepatic damage among the various metiglinides.  Reexposure and use of other metiglinides after clinically apparent liver injury related to nateglinide should be done with caution.

References regarding the safety and hepatotoxicity of nateglinide and repaglinide are given with the Overview section on the Metiglinide Analogues.

Drug Class:  Antidiabetic Agents

 

Other Drugs in the Subclass Metiglinide AnaloguesRepaglinide

 

Top of page


PRODUCT INFORMATION
Nateglinide

 

REPRESENTATIVE TRADE NAMES
Nateglinide – Generic, Starlix®

 

DRUG CLASS
Antidiabetic Agents

 

COMPLETE LABELING

Product labeling at DailyMed, National Library of Medicine, NIH


Top of page


DRUG CAS REGISTRY NUMBER MOLECULAR FORMULA STRUCTURE
Nateglinide 105816-04-4 C19-H27-N-O3 Nateglinide Chemical Structure

Top of page


OTHER REFERENCE LINKS
Nateglinide
  1. PubMed logoRecent References on Nateglinide

  2. Clinical Trials logoTrials on Nateglinide

Top of page