Rosiglitazone (DB00412): A Comprehensive Pharmacological, Clinical, and Regulatory Review

Introduction

Rosiglitazone is an oral antidiabetic agent belonging to the thiazolidinedione (TZD) class of drugs, developed by GlaxoSmithKline and marketed principally under the trade name Avandia.[1] Its primary therapeutic action is as an insulin sensitizer, designed to improve glycemic control in adult patients with type 2 diabetes mellitus by enhancing the responsiveness of peripheral tissues to endogenous insulin.[1] The clinical narrative of Rosiglitazone is defined by a profound and enduring conflict between its established efficacy in lowering blood glucose and the severe, controversial safety concerns that ultimately precipitated its clinical and commercial decline. This dichotomy is centered on the drug's association with significant cardiovascular adverse events, particularly congestive heart failure and a contentious signal for increased risk of myocardial infarction.[1]

These safety concerns ignited a decade-long, highly public scientific and regulatory debate, culminating in historic and divergent actions by the world's leading drug regulatory agencies. Both the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) subjected Rosiglitazone to intense scrutiny, resulting in market suspension in Europe and severe use restrictions in the United States.[8]

This report provides a comprehensive review of Rosiglitazone, serving as a case study that analyzes its journey from a promising therapeutic agent to a cautionary tale in modern pharmacovigilance. It will explore the drug's molecular and physicochemical properties, its pharmacological mechanism of action, and its clinical application. Critically, it will dissect the scientific controversies it engendered, the evolution of its safety profile, and its lasting legacy on the regulatory standards for drug approval, particularly for new antidiabetic medications.[11]