From the Guidelines
Thiazolidinediones, such as pioglitazone and rosiglitazone, are the primary examples of this class of oral medications used to treat type 2 diabetes by improving insulin sensitivity. These medications work by activating peroxisome proliferator-activated receptor gamma (PPAR-γ), which regulates genes involved in fat and glucose metabolism 1.
Key Characteristics and Uses
- Typical dosing for pioglitazone ranges from 15-45 mg once daily, while rosiglitazone is usually prescribed at 4-8 mg daily, either as a single dose or divided into two doses 1.
- These medications are particularly useful for patients with insulin resistance and may be used alone or in combination with other antidiabetic drugs like metformin or sulfonylureas.
- Patients should be aware that thiazolidinediones may cause fluid retention, weight gain, and increased risk of heart failure, so they require regular monitoring 1.
Important Considerations
- They typically take 2-3 months to reach their full glucose-lowering effect, and patients should continue other diabetes management strategies including diet and exercise while taking these medications.
- The use of thiazolidinediones has been associated with an increased risk of fractures and heart failure, and their use is contraindicated in patients with 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.
Recent Guidelines and Recommendations
- Recent studies have shown that pioglitazone can reduce cardiovascular end points, but without conclusive evidence for benefit 1.
- The American Heart Association recommends that thiazolidinediones be avoided or discontinued in patients with heart failure (Class III Recommendation: Harm; Level of Evidence B) 1.
- The use of rosiglitazone has been suspended by the European Medicines Agency and the Korea Food and Drug Administration due to the risk of complications 1.
From the FDA Drug Label
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.
Examples of thiazolidinediones include pioglitazone, as mentioned in the drug label 2.
- Key points about thiazolidinediones:
- They improve sensitivity to insulin in muscle and adipose tissue and inhibit hepatic gluconeogenesis.
- They can cause fluid retention, which can exacerbate or lead to congestive heart failure.
- They may result in ovulation in some premenopausal anovulatory women, increasing the risk for pregnancy. No other examples of thiazolidinediones are provided in the given drug labels.
From the Research
Examples of Thiazolidinediones
Characteristics of Thiazolidinediones
- Improve insulin sensitivity in adipose tissue, liver, and skeletal muscle 3
- Reduce glycated haemoglobin levels, fasting plasma glucose, insulin, and free fatty acids levels in subjects with Type 2 diabetes 3, 4
- Increase HDL cholesterol and decrease triglycerides (pioglitazone) 3, 4
- Increase total, low- and high-density lipoprotein (LDL and HDL) cholesterol, and triglycerides (rosiglitazone) 4
- Decrease inflammatory markers 4
- May cause a small decrease in blood pressure, improve endothelial function, and reduce restenosis 4
- May reduce microalbuminuria 4
Safety and Side Effects
- Liver function must be checked at baseline every second month for the first year, and periodically thereafter 3
- Contraindicated in patients with moderate to severe liver dysfunction and alanine aminotransferase levels more than 2.5 times normal, New York Heart Association III-IV cardiac status, pregnancy, lactation, and in children 3
- Main side effects include weight gain, oedema, and mild dilutional anaemia 3
- Cardiovascular events are currently the most serious adverse events of rosiglitazone 5
- Increased risk of heart failure, myocardial infarction, and fractures 5, 6