The Role of Kidney in Glucose Homeostasis — SGLT2 Inhibitors, a New Approach in Diabetes Treatment

Vasileios Andrianesis; John Doupis


Expert Rev Clin Pharmacol. 2013;6(5):519-539. 

In This Article

SGLT2 Inhibitors

Beginning With a Natural Product

The first inhibitor of Na/glucose co-transporter was isolated by French chemists from the bark of apple trees in 1835. This substance (phlorizin) that was firstly named 'glycoside from the bark of apple trees' was supposed to have similar properties with the extracts from the cinchona and willow tree. For this reason, phlorizin was used for the treatment of fever and infectious diseases, and only 50 years later, it was discovered that high doses of phlorizin caused glucosuria. In the beginning of the 20th century, it was observed that chronic administration of phlorizin in animal models caused many symptoms of diabetes (glucosuria, polyuria and weight loss), and for this reason,it was used for experimental induction of diabetes.[50] In the 1970s was first introduced the connection between phlorizin and the glucose reabsorption system of the proximal convoluted tubule,[51] and in the 1990s, the first description of SGLTs was introduced along with the idea of the development of a novel agent that would reduce the hyperglycemia through glucosuria.[52,53] However, the poor gastrointestinal absorption and the simultaneous inhibition of both SGLT2 and SGLT1 receptors excluded phlorizin from human use.