Insight Into the Recent Advancements in Thiazolidinedione Derivatives as PPAR-γ Agonists for the Treatment of Type 2 Diabetes.

INTRODUCTION: Thiazolidinediones, commonly known as glitazones, serve as a vital biological framework in the treatment of type 2 diabetes. This established class of medications works by lowering insulin resistance and improving the body's ability to utilize glucose in peripheral tissues. They achieve this by activating PPAR-γ, a PPAR subtype. Additionally, various hybrid PPAR- γ agonists have demonstrated multiple therapeutic effects, including antidiabetic activity. This review is designed to consolidate and evaluate current research regarding the therapeutic benefits and structure-activity relationship, synthesis, and both marketed and non-marketed thiazolidinedione analogues developed for treating type 2 diabetes over the past two decades. METHODS: To achieve this objective, a comprehensive search was conducted across various academic and legal databases such as PubMed, ScienceDirect, Google Scholar, and so on. The process involved synthesizing data from original research manuscripts, review articles, and patent filings from 2016 to 2026, which were then critically analyzed. RESULT: The thiazolidinedione scaffold has been a key focus in research on biological activity and the synthesis of novel derivatives for managing type 2 diabetes, particularly in treating insulin resistance. DISCUSSION: However, complications such as fluid retention, idiosyncratic hepatotoxicity, weight gain, and CHF associated with rosiglitazone and pioglitazone have limited their use. To improve efficacy and reduce side effects, various research groups have developed newer analogues. CONCLUSION: The potential of thiazolidinediones, regarding their chemical development and interaction with PPAR-γ receptors, is well known. Newer TZD analogues that offer enhanced safety and tolerability are anticipated to become widely accessible soon.