Abstract
Diabetes mellitus poses a significant and escalating burden on global public health. As a major breakthrough in glycemic control, sodium-glucose transporters (SGLT) inhibitors are now established as indispensable agents for managing type 2 diabetes. This status is evidenced by the continuously increasing market share in the antidiabetic agent market worldwide. The development of these inhibitors shows how leads from natural products ultimately evolved into clinically useful agents via structure-based drug design. Specifically, structural modifications to overcome the metabolic instability of phlorizin have yielded orally administrable SGLT inhibitors with improved pharmacokinetic profiles. This modification represents a shift towards more resource-efficient and sustainable molecular design. In recent years, these inhibitors have been found to have cardiorenal protective effects independent of glycemic status in clinical trials, thereby fundamentally altering their therapeutic positioning towards heart failure and chronic kidney disease. This article reviews the current market landscape and the evolutionary trajectory of SGLT inhibitors. Additionally, we discuss emerging R&D strategies, highlighting the role of computational drug design and structural biology in accelerating the identification of novel scaffolds. By leveraging these advanced methodologies, researchers can overcome current limitations in potency and selectivity. These approaches offer promising avenues for optimizing lead compounds and developing next-generation therapies with improved pharmacological profiles.