Akademik Veri Yönetim Sistemi
Experimental and Clinical Transplantation, cilt.21, sa.6, ss.105-108, 2023 (SCI-Expanded)
Diabetes has been acknowledged since ancient times. However, it was only during the late 1800s that we realized that the primary organ for blood glucose regulation was the pancreas. The 20th century witnessed insulin purification, which revolutionized the treatment of diabetes maigre; this was followed by the development of oral antidiabetic drugs. The sodium-glucose cotransporter 2 inhibitors or gliflozins are the latest class. Unique cardio-and renoprotective effects separate them from other oral antidiabetic drugs. Here, we present the history behind the development of these inhibitors, arguably the hottest and the most pleasant topic in nephrology. The first serendipity was Koninck and Stas (assistants to Prof. Van Mons, a renowned pomology expert); these researchers isolated a crystalline glycoside called phloridzin (phlorizin) from the bark of apple trees while working at their boss’s nursery. Their discovery was published in German in 1835. The second serendipity, after a half century, was from Prof. von Mering, who decided to administer phlorizin to dogs. Oskar Minkowski initially observed polyuria than glucosuria. Insightfully, von Mering postulated that phlorizin affects kidneys. In 1887, they reported that phlorizin induced glucosuria in people with diabetes. The third serendipity was that phlorizin causes several gastrointestinal side effects and has poor oral bioavailability. The first phlorizin-based drug to enter trials was T-1095. The first clinically available gliflozin was dapagliflozin, receiving approval in Europe and the United States in 2012 and 2014, respectively. The 2015 EMPA-REG Outcome trial reported extremely satisfying results that no one expected. Subsequent trials and real-world data have resulted in changes in all impactful guidelines. The impact of these agents on heart failure and chronic kidney disease seems independent of their antidiabetic properties. More than 100 years after von Mering’s original discovery, descendants of phlorizin are fast becoming the most inspiring medicine for the 21st century physician.