rosiglitazones

Rosiglitazone is a thiazolidinedione antidiabetic agent that acts as a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist. It improves insulin sensitivity in adipose tissue, muscle, and liver, lowering blood glucose in adults with type 2 diabetes. It was marketed as Avandia in many countries.

Mechanism: PPAR-γ activation modulates gene transcription involved in glucose and lipid metabolism, promoting adipogenesis and increasing insulin-stimulated glucose uptake. The result is reduced insulin resistance and lower hepatic glucose production.

Medical use: Rosiglitazone was approved as an add-on therapy to diet and exercise for adults with type 2 diabetes, usable alone or with other agents such as metformin, a sulfonylurea, or insulin when glycemic targets remained unmet. It is not indicated for type 1 diabetes or diabetic ketoacidosis.

Safety and regulation: The drug is associated with fluid retention, edema, weight gain, and congestive heart failure. Concerns about an increased risk of myocardial infarction and death led to regulatory actions in several regions. In the United States, the FDA imposed labeling changes and an approved restricted-use program; in the European Union, rosiglitazone was suspended or withdrawn from the market. As a result, many clinicians now prefer other thiazolidinediones or alternative glucose-lowering therapies.

History: Rosiglitazone was approved by the U.S. FDA in 1999 and marketed as Avandia. Ongoing cardiovascular safety reviews have limited its availability in many jurisdictions.