Thiazolidinediones
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Information about Thiazolidinediones[edit source]
The thiazolidinediones are a relatively new family of agents for type 2 diabetes that act by increasing insulin sensitivity through a unique mechanism of engagement of the so-called peroxisome proliferator-activated receptor gamma, PPAR-?. Attachment of ligand to the PPAR-? receptor activates a series of genes that are involved in glucose and fatty acid metabolism, the overall effect being an increase in insulin effect.
Mechanism of action of Thiazolidinediones[edit source]
The thiazolidinediones reduce blood glucose levels in patients with type 2 diabetes and act additively with other antidiabetic medications. Troglitazone was the first thiazolidinedione that received approval for use in the United States (January 1997). However, within a year of its approval, reports of severe liver injury and deaths from acute liver failure began to appear. Cautionary statements and recommendations for monitoring of ALT levels were made, but after more than two dozen reports of hepatic failure and the introduction of two new thiazolidinediones in 1999, troglitazone was withdrawn from use in 2000. The newer thiazolidinediones, rosiglitazone and pioglitazone, have been associated with only rare instances of acute liver injury.
Liver safety of Thiazolidinediones[edit source]
Both rosiglitazone and pioglitazone are linked to increased weight gain, heart failure and fracture risk and they are considered second-line agents for type 2 diabetes and recommended only after failure of metformin and lifestyle modifications.
Drug class for Thiazolidinediones[edit source]
Drug Class: Antidiabetic Agents
Drugs in the Subclass, Thiazolidinediones: Pioglitazone, Rosiglitazone, Troglitazone
Antidiabetics
- Alpha-Glucosidase Inhibitors
- Incretin-Based Drugs
- Insulin
- Metformin
- Metiglinide Analogues
- Pramlintide
- Sodium Glucose Cotransporter-2 (SGLT-2) Inhibitors
- Sulfonylureas
- First Generation Sulfonylureas
- Acetohexamide
- Chlorpropamide
- Tolazamide
- Tolbutamide
- Second Generation Sulfonylureas
- Gliclazide
- Glimepiride
- Glipizide
- Glyburide (Glibenclamide)
- First Generation Sulfonylureas
- Thiazolidinediones
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Contributors: Prab R. Tumpati, MD
