Thiazolidinediones

Thiazolidinediones are a class of oral antidiabetic drugs that act as agonists of the peroxisome proliferator-activated receptor gamma (PPAR-γ). Activation of PPAR-γ improves insulin sensitivity in adipose tissue, skeletal muscle, and the liver, leading to lower insulin resistance and reduced hepatic glucose production. In general, they lower hemoglobin A1c and fasting glucose when added to other antidiabetic therapies.

The two main agents currently in clinical use are pioglitazone and rosiglitazone. Troglitazone, the first in the class, was withdrawn from the market because of severe liver toxicity. Rosiglitazone has faced scrutiny for potential cardiovascular risks in some studies and has had restricted labeling in certain regions. Pioglitazone has been associated with an increased risk of bladder cancer in some observational studies, which has led to warnings in various regulatory texts.

Clinical use and cautions: TZDs are typically added to metformin or a sulfonylurea when glycemic control remains above target. They may be used in combination with insulin in selected patients. They are generally not first‑line due to risks such as weight gain, fluid retention, and edema, and they are avoided in patients with symptomatic heart failure or significant liver disease. They require regular monitoring, including baseline and periodic liver function tests, and discontinuation if signs of liver injury or severe adverse effects occur.

Pharmacokinetics and safety notes: TZDs are orally active and undergo hepatic metabolism. They may cause weight gain, edema, and an increased risk of fractures, particularly in long-term use. Liver toxicity was a major issue with troglitazone, informing current monitoring practices for the remaining TZDs.