Treatment Response to SGLT2 Inhibitors: From Clinical Characteristics to Genetic Variations

Abstract

SGLT2 (sodium-glucose cotransporter 2) inhibitors are a new class of antihyperglycaemic drugs that act on the proximal tubules of the kidney. They have shown efficacy in the management of diabetes mellitus type 2 and their cardiovascular and renal safety have been extensively investigated and confirmed in clinical trials. However, inter-individual differences in response to treatment with SGLT2 inhibitors may present in everyday clinical practice, and good predictors of glycemic response and the risk for adverse events in an individual patient are lacking. As genetic variability of SGLT2 may influence the treatment response, pharmacogenetic information could support the choice of the most beneficial treatment strategy in an individual patient. This review focuses on the clinical and genetic factors that may influence the treatment response to SGLT2 inhibitors in type 2 diabetes patients with comorbid conditions.

Case report: Identification of three novel compound heterozygous SGLT2 variants in three Chinese pediatric patients with familial renal glucosuria

“…In general, severe clinical consequences have not been observed in patients of FRG, which, therefore, is usually considered to be a benign condition (4,(12)(13)(14). Intriguingly, research on SGLT2 mutations-associated FRG have received a great of attention, as SGLT2 inhibitors, which usually show minimal side effects and include canagliflozin, dapagliflozin, and empagliflozin, have been clinically used to lower blood glucose level in patients with type 2 diabetes and are also showing promising potential for treatment of other diseases, such as cardiovascular disorders (15-17).…”

Sodium‐glucose cotransporter 2 inhibitors: A comprehensive review from cells to bedside

“…1 SGLT2s are responsible for 90% of glucose reabsorption and are mostly found on the luminal surface of proximal convoluted tubules of the kidney as well as the small intestine. 1 Also, SGLT2is are involved in glucose metabolism through several signaling pathways and hormonal interactions. 2 In addition to their roles in the glucose homeostasis, SGLT2is provide protective effects for cardiovascular and renal systems.…”

“…2 In addition to their roles in the glucose homeostasis, SGLT2is provide protective effects for cardiovascular and renal systems. 1,3 Phlorizin, an O-glucoside of phloretin, was the first natural compound with SGLT2 inhibitory effects and was primarily isolated from the apple tree, mostly from its vegetative tissues, about 2 centuries ago. Later, it was shown to be able to inhibit both SGLT1 and SGLT2.…”

“…Sodium‐glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) are a rather newly introduced class of antidiabetic agents that provide hypoglycemic effects by overt urinary glucose excretion through SGLT2 inhibition 1 . SGLT2s are responsible for 90% of glucose reabsorption and are mostly found on the luminal surface of proximal convoluted tubules of the kidney as well as the small intestine 1 . Also, SGLT2is are involved in glucose metabolism through several signaling pathways and hormonal interactions 2 .…”

Editorial to the IJMS Special Issue on Sglt2 Inhibitors Vol. 1

“…Finally, a couple of reviews included in the Special Issue discussed the vascular effects of SGLT2 inhibitors [ 7 ] and their safety from a pharmacogenetic standpoint [ 8 ]. Regarding the vascular benefits and mechanisms of SGLT2 inhibitors, these drugs enhance the bioavailability of endothelium-derived nitric oxide, restoring endothelium-dependent vasodilation in diabetes [ 7 ].…”