thiazolidinedione

Thiazolidinedione (TZD) refers to a class of oral medications used to improve glycemic control in type 2 diabetes. The principal agents are pioglitazone and rosiglitazone. TZDs are agonists of peroxisome proliferator-activated receptor gamma (PPAR-γ), which modulates transcription of genes involved in glucose and lipid metabolism.

Mechanism: Activation of PPAR-γ increases insulin sensitivity in adipose tissue, skeletal muscle, and liver, promotes adiponectin production, and reduces hepatic glucose production. The net effect is better peripheral glucose uptake and lower fasting glucose and HbA1c. Clinical effects typically emerge over weeks.

Clinical use: TZDs are used as add-on therapy in adults with type 2 diabetes, often with metformin, a sulfonylurea, or insulin. They are not for type 1 diabetes or diabetic ketoacidosis. Dosing varies by agent: pioglitazone typically 15–30 mg daily (up to 45 mg), rosiglitazone 4–8 mg daily in divided doses; liver function tests are recommended.

Safety and adverse effects: Common adverse effects include weight gain and edema; fluid retention can worsen heart failure and TZDs are contraindicated in symptomatic heart failure. Other risks include bone fractures, particularly in women, and hepatic injury with older agents. Pioglitazone has been linked to a possible increased risk of bladder cancer in some studies; rosiglitazone has been associated with cardiovascular risk, leading to regulatory restrictions in some regions. Monitor liver enzymes and use with caution in patients with cardiovascular risk.