Molecular mechanisms by which SGLT2 inhibitors can induce insulin sensitivity in diabetic milieu: A mechanistic review

Abstract

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) are a relatively newer class of anti-hyperglycemic medications that reduce blood glucose by inhibition of renal glucose re-uptake, thereby increasing urinary glucose excretion. Although glycosuria is the primary mechanism of action of these agents, there is some evidence suggesting they can reduce insulin resistance and induce peripheral insulin sensitivity. Identifying the molecular mechanisms by which these medications improve glucose homeostasis can help us to develop newer forms of SGLT2i with lesser side effects. We have reviewed the molecular mechanisms and signaling pathways by which SGLT2i therapy improve insulin sensitivity and ameliorates insulin resistance.

Keywords: Diabetes mellitus; Inflammatory response; Insulin resistance; Insulin sensitivity; Oxidative stress; Sodium-glucose co-transporter-2 inhibitors.