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Thiazolidinediones can be used in combination with other drugs that treat type 2 diabetes to decrease insulin resistance and glucose production. These drugs can also be alternative medications for clients who are overweight or have a risk of hypoglycemia. They are also useful agents for clients with...

Thiazolidinediones can be used in combination with other drugs that treat type 2 diabetes to decrease insulin resistance and glucose production. These drugs can also be alternative medications for clients who are overweight or have a risk of hypoglycemia. They are also useful agents for clients with medication cost or access issues. Overview of the Drug Class **Prototype: pioglitazone (Actos) ** - **Category**: Thiazolidinediones (Oral Hypoglycemic Agent)  - **Primary Function**: Thiazolidinediones, known as glitazones, reduce glucose levels by decreasing insulin resistance and production. These drugs can also be alternative medications for clients who are overweight or have a risk of hypoglycemia. They are also useful agents for clients with medication cost or access issues.  - **Unique Features**: Thiazolidinediones are frequently used with other drugs to treat type 2 diabetes. Recently, the FDA placed restrictions on thiazolidinediones due to evidence linking their use to MI and sudden cardiac death.  Mechanism of Action - Thiazolidinediones activate the peroxisome proliferator-activated receptor gamma (PPAR gamma) in the cell nucleus, which activates insulin-responsive genes regulating carbohydrate and lipid metabolism. This activation increases cellular insulin sensitivity, especially in skeletal muscle and adipose cells, and mildly reduces liver glucose production.  Indications and Therapeutic Uses - **Diabetes**: Thiazolidinediones are utilized to improve glycemic control in clients with type 2 diabetes. Side Effects and Adverse Reactions **Side Effect** **Description** ----------------- -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Heart Failure Thiazolidinediones have a black box warning for this condition, which can be precipitated or exacerbated secondary to fluid retention. Hypoglycemia With monotherapy, this risk is low. When combined with other agents to reduce blood sugar (such as insulin or other oral antidiabetic medications), this risk increases. Ovulation In premenopausal women, thiazolidinediones can cause this, potentially causing unintended pregnancy. Bladder Cancer With prolonged, high doses, thiazolidinediones can cause this, manifested by blood in the urine, painful urination, or increased urgency. Fractures This risk can increase in women, and the risk increases with long-term, high-dose therapy. Clients should take vitamin D and calcium and ensure adequate exercise and medications for osteoporosis, if applicable. Liver Failure Although rare, providers should monitor LFTs to ensure this side effect is not occurring before and during therapy. Precautions and Contraindications **Precautions** - Use with caution in clients with mild heart failure.  - Use caution in premenopausal women due to the risk of unintended pregnancy.  - Use caution in clients with elevated LDL cholesterol, as thiazolidinediones can increase LDL levels.  - Use caution in clients prone to hypoglycemia.  **Contraindications** - Contraindicated in clients with severe heart failure.  - Contraindicated in clients with a history of bladder cancer.  **Black Box Warning** - Thiazolidinediones can cause or exacerbate heart failure due to fluid retention.  Drug Interactions - Combining thiazolidinediones with **\[insulin\]** increases the risk of heart failure due to fluid retention.  - Thiazolidinediones are metabolized by the CYP2C8 enzyme in the liver. Combining thiazolidinediones with drugs that inhibit CYP2C8, such as **\[atorvastatin or ketoconazole\]**, can increase thiazolidinedione levels, necessitating a reduction in dosage. Combining thiazolidinediones with drugs that induce CYP2C8, such as **\[rifampin or cimetidine\]**, can reduce thiazolidinedione levels, necessitating an increase in dosage.   Dosing, Administration, & Client Teaching **Dosing** - Dosing varies based on the condition, severity, and client response.  - Check drug dosing guidelines for individualized dosing.  - PO dosing, once daily.  - Practice careful client selection to prevent adverse effects.  - These drugs can also be alternative medications for clients who are overweight or have a risk of hypoglycemia. They are also useful agents for clients with medication cost or access issues.  - These medications can also be used in clients who also have a history of stroke or TIA.  **Administration** - PO administration.  **Client Teaching** - Clients should regularly monitor their blood glucose levels to avoid hypoglycemia.  - Clients should be educated in recognizing the signs and symptoms of hypoglycemia and how to manage it should it occur.  - Educate premenopausal women about the importance of contraception to avoid unintended pregnancy.  - Educate clients about adverse effects, including signs and symptoms of heart and liver failure.  Labs to Monitor **Liver Function Tests (LFTs)** - LFTs should be assessed at baseline and throughout therapy.  **Lipid Profiles** - These drugs can increase LDL blood levels, requiring monitoring in some clients.  **Hemoglobin A1c** - Monitoring hemoglobin A1c will provide information on the effectiveness of the treatment regimen.