Troglitazone

What is Troglitazone

NOTE: This drug is discontinued in the US.

Troglitazone was an oral antidiabetic agent of the thiazolidinedione class, a group of drugs called ‘insulin sensitizers’.

Troglitazone specifically targeted insulin resistance and decreased both fasting and postprandial blood glucose in adult patients with type 2 diabetes mellitus (DM).

This drug was suspended from marketing in the United Kingdom in December 1997 due to concerns related to drug-induced hepatotoxicity. With the FDA approval of newer, safer thiazolidinediones (e.g., pioglitazone and rosiglitazone) in 1999, troglitazone was limited to use in type 2 DM patients who were unresponsive to other available therapies.

More than 90 cases of fulminant hepatotoxicity, including at least 63 deaths, were reported in association with the use of the drug. Due to concerns regarding drug safety and the availability of other agents in this class, the FDA and the manufacturer withdrew troglitazone from the U.S. market in March 2000.

Mechanism of Action

Troglitazone decreases hepatic glucose output by inhibiting gluconeogenesis and enhances the uptake of glucose by skeletal muscle cells.

Plasma glucose and insulin are subsequently reduced.

Troglitazone’s unique mechanism of action is dependent on the presence of insulin, however, the exact mechanism of action is unknown.

Troglitazone, and other thiazolidinediones, are believed to achieve their insulin sensitizing effects by serving as ligands for the transcription factor peroxisome proliferator activated receptor (PPAR-gamma) which regulates the transcription of a number of insulin responsive genes.

These genes encode for proteins important in controlling carbohydrate and lipid metabolism. Unlike oral sulfonylureas, troglitazone enhances the action of insulin rather than stimulates insulin secretion.

Both troglitazone and oral sulfonylureas are ineffective in patients with insulin deficiency (e.g., type 1 diabetes mellitus).

Troglitazone also reduces fasting triglyceride concentrations possibly by decreasing lipid synthesis in the liver and increasing lipid clearance from the circulation.

Indications & Dosage

• type 2 diabetes mellitus

For the treatment of type 2 diabetes mellitus in patients inadequately controlled by other available medications

Side Effects

1. abdominal pain
2. anorexia
3. asthenia
4. back pain
5. elevated hepatic enzymes
6. fatigue
7. headache
8. heart failure
9. hepatic failure
10. hypercholesterolemia
11. jaundice
12. nausea
13. peripheral edema
14. pharyngitis
15. vomiting
16. weight gain

Monitoring Parameters

• (drug no longer available)
• blood glucose
• LFTs

Contraindications

• breast-feeding
• children
• diabetic ketoacidosis
• heart failure
• hepatic disease
• jaundice
• polycystic ovary syndrome
• pregnancy

Interactions

No information is available regarding drug interactions associated with Troglitazone