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Thiazolidinediones (TZDs) are oral antidiabetic medicines that are primarily used to treat type 2 diabetes. These medications target PPAR-γ, a nuclear receptor that regulates glucose and lipid metabolism. Rosiglitazone and pioglitazone are the two most common thiazolidinediones on the market today. Both medicines work by improving insulin sensitivity in peripheral tissues including muscle and adipose tissue. These medicines activate PPAR-γ, which improves insulin-mediated glucose uptake and utilization, leading to better glycemic control. One of the primary methods by which thiazolidinediones work is to promote adipocyte differentiation and decrease adipocyte death. This leads in increased adipose tissue bulk and altered adipokine secretion patterns, which improves insulin sensitivity. Furthermore, thiazolidinediones lower hepatic glucose synthesis via controlling gene expression in the liver. Despite their effectiveness in managing glucose management, thiazolidinediones are not without risks. Adverse effects of these medications include weight gain, fluid retention, and an increased risk of heart failure. The latter has resulted in regulatory scrutiny and limitations on its use in certain countries. Furthermore, thiazolidinediones have been associated with an increased incidence of fractures, particularly in postmenopausal women. This has generated concerns about their long-term safety, necessitating careful examination of the possible advantages and hazards before administering these drugs. In recent years, thiazolidinediones have been replaced by alternative antidiabetic medicines with better safety profiles. However, they continue to play a role in certain therapeutic circumstances, particularly when other oral antidiabetic drugs fail to provide effective glycemic control. Thiazolidinediones are a type of oral antidiabetic medication that targets PPAR-γ, improving insulin sensitivity and glucose metabolism. While they are successful in controlling type 2 diabetes, their use raises concerns about potential side effects, particularly heart failure and fractures.