Turning Glucosuria into a Therapy: Efficacy and Safety with SGLT2 Inhibitors

Abstract

Hyperglycemia is important in the development of microvascular and macrovascular complications from type 2 diabetes. Although there are many oral therapies available to help ameliorate hyperglycemia, it has been found that the competitive inhibition of the sodium-D-glucose cotransporter-2 (SGLT2) in the kidney may be a promising alternative treatment reducing hyperglycemia and potentially helping to lower the risk of diabetes complications. This article reviews clinical trials that have revealed favorable responses to many glycemic and metabolic parameters with SGLT2 inhibition, both as monotherapy and as an adjunct to insulin and oral antidiabetic agents. Additional studies are necessary to further determine the efficacy and long-term safety of SGLT2 inhibitors.

Safe and pragmatic use of sodium–glucose co-transporter 2 inhibitors in type 2 diabetes mellitus: South Asian Federation of Endocrine Societies consensus statement

“…Osmotic diuresis, mild natriuresis, changes in nitric oxide release, and reductions in arterial stiffness contribute to lowering of BP. [115116117118] Unlike the GLP-1 RAs, the SGLT2i do not trigger an increase in heart rate, despite reductions in BP. [40119]…”

Pharmacokinetics, Metabolism, and Excretion of the Antidiabetic Agent Ertugliflozin (PF-04971729) in Healthy Male Subjects

“…Because of their ability to increase urinary glucose excretion in T2DM, SGLT2 inhibitors offer the advantage of plasma glucose-lowering without inducing excessive insulin secretion (Katsuno et al, 2007;Fujimori et al, 2008;Wilding et al, 2009;Patel and Fonseca, 2010). Furthermore, the increase in urinary glucose excretion leads to a negative energy balance and osmotic diuresis, making it a unique antidiabetic agent that reduces also body weight and blood pressure in diabetic patients (Abdul-Ghani and DeFronzo, 2008;Nair and Wilding, 2010).…”

Cardiovascular outcomes of sodium-glucose cotransporter 2 inhibitors: A comprehensive review of clinical and preclinical studies

“…Two SGLT isoforms have been identified: SGLT2, which is expressed on the brush border of epithelial cells of proximal renal tubules (mainly in S1 and S2 segments) and SGLT1, which is expressed primarily in the small intestine, the S3 segment of the proximal tubule of the kidney, and myocardium ( Fig. 1) [21]. Normally the kidneys filter of about 160-180 g of glucose each day.…”