Role of Sodium-Glucose Cotransporter 2 (SGLT 2) Inhibitors in the Treatment of Type 2 Diabetes

Abstract

Hyperglycemia plays an important role in the pathogenesis of type 2 diabetes mellitus, i.e., glucotoxicity, and it also is the major risk factor for microvascular complications. Thus, effective glycemic control will not only reduce the incidence of microvascular complications but also correct some of the metabolic abnormalities that contribute to the progression of the disease. Achieving durable tight glycemic control is challenging because of progressive β-cell failure and is hampered by increased frequency of side effects, e.g., hypoglycemia and weight gain. Most recently, inhibitors of the renal sodium-glucose cotransporter have been developed to produce glucosuria and reduce the plasma glucose concentration. These oral antidiabetic agents have the potential to improve glycemic control while avoiding hypoglycemia, to correct the glucotoxicity, and to promote weight loss. In this review, we will summarize the available data concerning the mechanism of action, efficacy, and safety of this novel antidiabetic therapeutic approach.

Pharmacokinetics of Empagliflozin, a Sodium Glucose Cotransporter 2 Inhibitor, and Glimepiride Following Co-administration in Healthy Volunteers: A Randomised, Open-label, Crossover Study

“…Despite a range of treatments available, only half of patients with type 2 diabetes achieve the recommended HbA 1c target [19]. Most anti-diabetic agents lower blood glucose levels via an insulin-dependent mechanism; however, due to the progressive nature of beta-cell dysfunction in type 2 diabetes [1], the efficacy of these agents is compromised over time [2]. A combination of two or more classes of anti-diabetic agent is more likely to achieve long-term glycaemic control in patients with type 2 diabetes compared to monotherapy [20].…”

“…Although the understanding of type 2 diabetes pathogenesis continues to evolve, the disease is known to be characterised by beta-cell dysfunction and progressive insulin resistance [1]. This progressive nature of the disease is known to cause the gradual loss of efficacy in existing therapies [2].…”

“…Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of medications being developed as treatments for type 2 diabetes [1]. In healthy individuals, approximately 180 g of glucose per day is filtered by the kidney and this is almost completely reabsorbed back into the bloodstream [5].…”

Drug–Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus

“…Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) are new glucoselowering agents, which specifically target the kidney by blocking the reabsorption of filtered glucose, thus leading to glucosuria [16,17] . This mechanism of action holds potential promise for patients with T2DM not only in terms of improvements in glycaemic control, but also considering the potential benefits of weight loss and arterial blood pressure reduction [16,17] .…”

Effect of canagliflozin, a sodium–glucose cotransporter 2 inhibitor, on measurement of serum 1,5‐anhydroglucitol (坎格列净，一种钠‐葡萄糖共转运体2抑制剂，对血清1,5‐脱水葡萄糖醇测定的影响)

“…The SGLT2 inhibitors decrease plasma glucose in patients with hyperglycemia by inhibiting renal glucose reabsorption via SGLT2 (the primary renal transporter responsible for reabsorption of glucose from the urine), thereby increasing urinary glucose excretion. 5 1,5-anhydroglucitol is transported by SGLT4, but there are no known interactions between 1,5-AG and SGLT2. Interference with the 1,5-AG assay by SGLT2 inhibitors may lead to falsely low serum 1,5-AG measurements in patients with improved glycemic control who are treated with this class of agent.…”