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

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.

The Effect of Empagliflozin on Platelet Function Profiles in Patients with Stable Coronary Artery Disease in Trinidad: The EFFECT Pilot Study

“…Recently, SGLT2is have gained robust traction as a novel class of antidiabetic agents with a unique mechanism of decreasing hyperglycemia by inducing glucosuria [12]. It does this chiefly by inhibiting the sodium-glucose cotransporter 2 proteins, which resorb glucose in the proximal convoluted tubule of the nephron [13]. In addition to its primary effect, natriuresis, weight loss, antihypertensive, and antilipidemic effects also occur [4].…”

A comparative <i>in vitro</i> study on the effect of SGLT2 inhibitors on chemosensitivity to doxorubicin in MCF-7 breast cancer cells

“…Recent research has indicated that CAN, DAP, and EMP have potential non-hypoglycemic benefits, such as cardiovascular protection [ 21 ], reduction of inflammation [ 22 ], and inhibition of tumor growth. Further, it was also reported that the combination of SGLT2i with DOX has a cardioprotective effect [ 23 ] In the current investigation, the co-administration of the medications CAN and DOX demonstrated heightened antitumor efficacy and a modest augmentation of the cytotoxicity of DOX.…”

Neutral effect of SGLT2 inhibitors on lipoprotein metabolism: From clinical evidence to molecular mechanisms

“…beyond renal inhibition of glucose reabsorption, suggesting that this class of drugs may work also through additional pleiotropic mechanisms. Indeed, the beneficial effect of SGLT2 inhibition extends beyond glycaemic control and not only includes protection from heart failure, but also the improvement in blood pressure, body weight, uric acid concentrations, liver steatosis, oxidative stress, and inflammation [70,71]. These observations would suggest extending the indication of SGLT2i also to subjects with metabolic syndrome thanks to the possibility of concomitantly controlling multiple metabolic alterations.…”