Exploring novel pharmacotherapeutic applications and repurposing potential of sodium glucose CoTransporter 2 inhibitors

Clin Exp Pharmacol Physiol. 2018 May 11. doi: 10.1111/1440-1681.12963. Online ahead of print.

Abstract

Sodium glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of anti-hyperglycaemic drugs with a distinctive mechanism of action focusing on renal absorption of glucose. Apart from its anti-hyperglycaemic effects, a multitude of research studies on this class have revealed that these drugs have far more versatile and comprehensive pharmacological effects than previously believed. Approximately 30% of FDA approved drugs are repurposed and used for indications other than those for which they were initially intended. Repurposing already approved drugs leads to significant reduction in pre-clinical and clinical R&D costs as well as minimizing the burden with respect to obtaining regulatory approval. SGLT2 inhibitors have been found to exhibit cardioprotective, renoprotective, anti-hyperlipidaemic, anti-atherosclerotic, anti-obesity, anti-neoplastic, hepatoprotective, and renoprotective effects in in vitro, pre-clinical, and clinical studies. The pleiotropic effects of this class have been attributed to a variety of its pharmacodynamic actions such as natriuresis, haemoconcentration, deactivation of RAAS, ketone body formation, alterations in energy homeostasis, glycosuria, lipolysis, anti-inflammatory, and anti-oxidative actions. These favourable observations encourage further research on this multifaceted class in order to effectively explore and harness its full potential and consequently lead to clinical outcomes.

Keywords: SGLT2; cardiovascular; hepatic; non-alcoholic steatohepatitis; obesity; renal; sodium glucose cotransporter 2 inhibitors.

Publication types

  • Review