Abstract
EMPAGLIFLOZIN AS POTENTIAL INHIBITOR OF POLYOL PATHWAY IN DIABETIC RETINOPATHY THROUGH SODIUM-GLUCOSE CO-TRANSPORTER-2 AS AN ACTIVATOR OF NITRIC OXIDE SYNTHASE

Kushal Nandi, *Dr. Dhrubo Jyoti Sen and Dr. Dhananjoy Saha

ABSTRACT

Empagliflozin is an inhibitor of sodium-glucose co-transporter-2 (SGLT2), the transporters primarily responsible for the reabsorption of glucose in the kidney. It is used clinically as an adjunct to diet and exercise, often in combination with other drug therapies, for the management of type 2 diabetes mellitus. The first known inhibitor of SGLTs, phlorizin, was isolated from the bark of apple trees in 1835 and researched extensively into the 20th century, but was ultimately deemed inappropriate for clinical use given its lack of specificity and significant gastrointestinal side effects. Attempts at overcoming these limitations first saw the development of O-glucoside analogs of phlorizin (e.g. remogliflozin etabonate), but these molecules proved relatively pharmacokinetically unstable. The development of C-glucoside phlorizin analogs remedied the issues observed in the previous generation, and led to the FDA approval of canagliflozin in 2013 and both dapagliflozin and empagliflozin in 2014. As the most recently approved of the "flozin" drugs, empagliflozin carries the highest selectivity for SGLT2 over SGLT1 (approximately 2700-fold).

Keywords: Polyol pathway, Aldose reductase inhibitor, SGLT2 inhibitor, Sorbitol, Sorbitol dehydrogenase, Retinopathy, Pyran, Oxolan.


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