Editorial: The role of sodium-glucose cotransporter 2 inhibitors in the management of chronic kidney disease
Abstract
The kidneys play an important role in maintaining glucose homoeostasis through the production of glucose via gluconeogenesis. They not only filter and reabsorb plasma glucose, but also use glucose as a metabolic fuel. These physiologic processes have been studied for a long time but have become an area of renewed and intense research interest in recent years as a result of the benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in reducing cardiovascular outcomes and delaying the progression of chronic kidney disease (CKD) in patients with type 2 diabetes. The kinetics of glucose reabsorption was first studied in the early 1930s [1]. These early studies demonstrated that renal glucose transport in the tubules can reach a maximum beyond which glucose is excreted in the urine. Wright et al. [2] demonstrated in the 1990s that the SGLT1 and SGLT2 transporters are responsible for the glucose reabsorption in the proximal tubule. Phlorizin was the first inhibitor of the SGLT transporters, but it never entered clinical practice due to its gastrointestinal side effects and metabolism to phloretin, which inhibits glucose transporters. Phlorizin’s poor tolerability and the molecular characterization of the SGLT transporters in the 1990s stimulated further development of small molecules that selectively inhibit the SGLT2 transporter. Interestingly, in hindsight, early studies demonstrated the potential of first-generation SGLT2 inhibitors to slow CKD progression. The first…
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