What are Thiazolidinediones (TZD) medications for diabetes?

From the Guidelines

Thiazolidinediones (TZDs) for diabetes include pioglitazone (Actos) and rosiglitazone (Avandia), which are the primary TZD medications available, as indicated in the most recent and highest quality study 1. These medications work by increasing insulin sensitivity in muscle and fat tissues while reducing glucose production in the liver.

Key Points

• The typical starting dose for pioglitazone is 15-30 mg once daily, which can be increased to a maximum of 45 mg daily if needed.
• Rosiglitazone is usually started at 4 mg daily (either as a single dose or divided into two 2 mg doses) and can be increased to 8 mg daily if necessary.
• TZDs may take 2-3 months to reach their full effect and are generally used as second or third-line agents in type 2 diabetes treatment.
• These medications are particularly useful for patients with insulin resistance and can be combined with other diabetes medications like metformin or sulfonylureas.

Side Effects and Considerations

• Side effects include fluid retention (which may worsen heart failure), weight gain, increased risk of bone fractures, and rarely, bladder cancer (with pioglitazone) 1.
• Liver function should be monitored before starting therapy and periodically thereafter, as TZDs were historically associated with liver concerns, though this is less common with current medications.
• Contraindications for TZDs include heart failure (New York Heart Association heart function classification class II and above), active liver disease, transaminase elevations exceeding 2.5 times the upper limit of normal, and severe osteoporosis and fractures 1.

From the FDA Drug Label

ACTOS is a thiazolidinedione antidiabetic agent that depends on the presence of insulin for its mechanism of action. Pioglitazone is a potent agonist for peroxisome proliferator-activated receptor-gamma (PPARγ). Pioglitazone [(±)-5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-] thiazolidinedione monohydrochloride belongs to a different chemical class and has a different pharmacological action than the sulfonylureas, metformin, or the α-glucosidase inhibitors.

The TZD (Thiazolidinedione) meds for diabetes are:

• Pioglitazone 2 2 These medications work by decreasing insulin resistance and improving sensitivity to insulin in muscle and adipose tissue.

From the Research

Thiazolidinediones (TZDs) for Diabetes

TZDs are a class of medications used to treat type 2 diabetes mellitus (T2DM) by improving insulin sensitivity. The following are some of the TZD medications:

• Pioglitazone 3, 4, 5, 6, 7
• Rosiglitazone 5, 6, 7

Mechanism of Action

TZDs work by activating peroxisome proliferator-activated receptors (PPARs), specifically PPARγ, which are predominantly expressed in adipose tissue 4.

Benefits and Side Effects

TZDs have been shown to:

• Improve glycemic control with a low incidence of hypoglycemia 3, 4
• Reduce vascular risk and inflammatory markers 4
• Improve carotid intima media thickness independent of their glycaemic effect 4
• Reduce myocardial infarctions and ischemic strokes 6 However, TZDs can also cause:
• Fluid retention, increasing the risk of heart failure 3, 4, 5, 7
• Edema, congestive heart failure, and bone fractures 6
• Increased risk of bladder cancer with pioglitazone 6