Sodium Glucose Cotransporter-2 Inhibitors: Spotlight on Favorable Effects on Clinical Outcomes beyond Diabetes

Abstract

Sodium glucose transporter type 2 (SGLT2) molecules are found in proximal tubules of the kidney, and perhaps in the brain or intestine, but rarely in any other tissue. However, their inhibitors, intended to improve diabetes compensation, have many more beneficial effects. They improve kidney and cardiovascular outcomes and decrease mortality. These benefits are not limited to diabetics but were also found in non-diabetic individuals. The pathophysiological pathways underlying the treatment success have been investigated in both clinical and experimental studies. There have been numerous excellent reviews, but these were mostly restricted to limited aspects of the knowledge. The aim of this review is to summarize the known experimental and clinical evidence of SGLT2 inhibitors’ effects on individual organs (kidney, heart, liver, etc.), as well as the systemic changes that lead to an improvement in clinical outcomes.

Relationship of vitamin D deficiency to cardiovascular disease and glycemic control in patients with type 2 diabetes mellitus: The Silesia Diabetes-Heart Project

“…Moreover, this class of drugs is increasingly used due to its glucose lowering and cardio-and nephroprotective benefits [42]; hence, its influence on VD concentrations and bone status seems important [43]. To the best of our knowledge, there are no trials designed solely to assess the association of the SGLT-2i treatment and VD concentrations, and the available results are acquired from trials assessing the SGLT-2i impact on bone health.…”

TorS ‐ Reframing a rational for type 2 diabetes treatment

“…Standard-of-care treatments of T2D, initially designed to control T2D hyperglycemia, appear now to be progressively indicated for the treatment of non-glycaemic diseases of T2D/MetS (e.g., obesity, heart failure, chronic kidney disease, NAFLD/nonalcoholic steatohepatitis (NASH), PCOS, neurodegeneration, cancer), independently of glucose lowering, and in non-T2D patients altogether. [28][29][30][31] Due to the current gluco/insulin-centric focus of T2D, the pleiotropic efficacy of concerned treatments is ascribed to an apparent linkage to insulin and/or the glycaemic and/or the lipaemic context of T2D/ MetS. Alternatively, the TorS paradigm maintains that the efficacy of current T2D SOC treatments may concomitantly be ascribed to suppression of hyperactive mTORC1 kinase activity, independently of the insulin/glycaemic/lipaemic context.…”

Heart Failure with Preserved Ejection Fraction and Obstructive Sleep Apnea: A Novel Paradigm for Additional Cardiovascular Benefit of SGLT2 Inhibitors in Subjects With or Without Type 2 Diabetes

“…Further evidence of the favorable effect on OSA pathophysiology comes from the proven effect of SGLT2is on visceral and subcutaneous adipose tissue [ 47 – 49 ]. As shown in animal models of T2DM and metabolic syndrome, the latter depends on the increased lipolysis and beta-oxidation of fatty acids [ 50 – 52 ] caused by a shift in energy substrates from carbohydrates to lipids [ 53 ].…”