Thiazolidinediones (TZDs), also known as “glitazones,” are a class of oral medications. They are primarily used to manage certain health conditions by improving how the body handles specific substances.
Understanding TZDs
TZDs are a class of oral antidiabetic drugs primarily used to treat type 2 diabetes. They are prescribed to improve blood sugar control in adults with this condition. These medications are often used as part of a broader treatment plan that includes diet, exercise, and weight reduction. TZDs can be used alone or in combination with other oral agents for type 2 diabetes, such as metformin or sulfonylureas, when these agents alone are not enough to control blood glucose levels. They are particularly helpful for individuals with type 2 diabetes who experience significant insulin resistance, a condition where the body’s cells do not respond effectively to insulin, leading to elevated blood sugar levels. By targeting this resistance, TZDs help the body’s own insulin work more efficiently.
How TZDs Work in the Body
The mechanism of action for TZDs involves activating specific nuclear receptors within cells, known as peroxisome proliferator-activated receptor-gamma (PPAR-gamma). These receptors are found predominantly in fat cells (adipocytes), but also in muscle and liver tissues. When TZDs bind to and activate PPAR-gamma, they influence the transcription of several genes involved in glucose and lipid metabolism. This activation leads to increased fatty acid storage in fat cells, reducing circulating free fatty acids and making cells more reliant on glucose for energy, thereby improving glucose uptake and utilization in muscle and fat tissue. TZDs also help decrease glucose production by the liver and can increase levels of adiponectin, a hormone secreted by fat tissue that enhances insulin sensitivity.
Examples of TZD Medications
Pioglitazone (Actos) and rosiglitazone (Avandia) are two commonly known TZD medications approved by the FDA. These medications are typically prescribed as oral tablets, taken once or twice daily, with or without food. While both work through similar mechanisms, their specific usage and availability can vary by region. For instance, rosiglitazone faced restrictions and was withdrawn from the market in some areas due to concerns, though some restrictions were later lifted.
Key Considerations for TZD Use
Potential Side Effects and Risks
Common side effects of TZDs include fluid retention, which can lead to swelling (edema) and weight gain. This fluid retention can also contribute to or worsen heart failure in some patients, requiring monitoring for signs like sudden weight gain or shortness of breath. TZD use is also associated with an increased risk of bone fractures, particularly in women. Additionally, pioglitazone has been linked to an increased risk of bladder cancer and should not be prescribed for patients with active bladder cancer. Liver function should be monitored regularly, especially during the first year of therapy, as newer TZDs have not shown the same severe liver toxicity as an earlier drug in this class.
Important Contraindications
TZDs are contraindicated for individuals with certain conditions, including symptomatic heart failure (NYHA Class III or IV) and active liver disease. They are not used for type 1 diabetes or diabetic ketoacidosis. Patients should discuss all existing health conditions and medications with their healthcare provider to determine if TZDs are a suitable treatment option and to understand the specific risks involved.