Recent Advances in the Development of Type 2 Sodium-Glucose Cotransporter Inhibitors for the Treatment of Type 2 Diabetes Mellitus

Abstract

Background: Type 2 diabetes mellitus (T2DM) is one of the most serious and prevalent diseases worldwide. In the last decade, type 2 sodium-glucose cotransporter inhibitors (iSGLT2) were approved as alternative drugs for the pharmacological treatment of T2DM. The anti-hyperglycemic mechanism of action of these drugs involves glycosuria. In addition, SGLT2 inhibitors cause beneficial effects such as weight loss, a decrease in blood pressure, and others. Objective: This review aimed to describe the origin of SGLT2 inhibitors and analyze their recent development in preclinical and clinical trials. Results: In 2013, the FDA approved SGLT2 inhibitors as a new alternative for the treatment of T2DM. These drugs have shown good tolerance with few adverse effects in clinical trials. Additionally, new potential anti-T2DM agents based on iSGLT2 (O-, C-, and N-glucosides) have exhibited a favorable profile in preclinical evaluations, making them candidates for advanced clinical trials. Conclusion: The clinical results of SGLT2 inhibitors show the importance of this drug class as new anti-T2DM agents with a potential dual effect. Additionally, the preclinical results of SGLT2 inhibitors favor the design and development of more selective new agents. However, several adverse effects could be a potential risk for patients.

The Protective Effects of Neurotrophins and MicroRNA in Diabetic Retinopathy, Nephropathy and Heart Failure via Regulating Endothelial Function

“…However, several observational studies fail to demonstrate a reduction in heart failure (HF) hospitalizations in diabetic patients treated with anti-hyperglycemic therapy [ 1 ]. On the other hand, in placebo-controlled trials, SGLT2i (sodium glucose transporter 2 inhibitors) reduced HF incidence [ 5 ]. In the meta-analysis, compared with placebo, HF risk showed a non-significant 10% reduction with the newer anti-hyperglycemic drugs (HR = 0.90, 0.80–1.01); use of DPP-4i and glucagon-like peptide-1-receptor-agonists GLP-1 RAs [ 6 ] was associated with nonsignificant modifications of the HF risk (+5% and −9%, respectively).…”