SGLT2 inhibitors, an Accomplished Development in Field of Medicinal Chemistry: an Extensive Review

Abstract

Diabetes is a chronic progressive metabolic disease caused by insulin deficiency or insulin resistance. In spite of the availability of several antihyperglycaemics, there is a need for the development of safer antidiabetic drugs due to their undesirable effects. Sodium-glucose cotransporter-2 inhibitors are a class of antidiabetics, which hinder the reabsorption of glucose in the kidneys, causing excretion of glucose via urine. Sodium-glucose cotransporter-2 inhibitors are a well-tolerated class with no significant adverse effects and are found to be favorable in certain conditions, which may be rudimentary to cardiovascular and renal diseases. The current advancements in their design and development, their mechanism of action, structure–activity relationship, synthesis and in silico development along with their auxiliary roles have been extensively reviewed.

Repurposing of Omarigliptin as a Neuroprotective Agent Based on Docking with A2A Adenosine and AChE Receptors, Brain GLP-1 Response and Its Brain/Plasma Concentration Ratio after 28 Days Multiple Doses in Rats Using LC-MS/MS

“…About 150 g of glucose is being filtered each day. However, per usual, these glucoses readily reabsorbed [81][82][83]. Glucose reabsorption is done over two steps, firstly at the basolateral membrane of proximal convoluted tubule.…”

The controversial therapeutic journey of chloroquine and hydroxychloroquine in the battle against SARS-CoV-2: A comprehensive review

“…These molecules have already passed all the hurdles of drug discovery processes. Comorbidities like cardiovascular diseases are to be considered because among the people affected by COVID-19, a huge number of them are elderly people, having other underlying diseases like cardiac and lifestyle disorders like diabetes [ 20 , [91] , [92] , [93] ]. General supporting treatments like electrolyte maintenance in the body and maintaining all vitals like heart rate, pulse rate, and respiratory rate is essential.…”

A Paradigm Shift for the Sglt2 Inhibitors – Treating the Heart With Anti-Hyperglycaemic Drugs

“…In the normal healthy adult, the kidney can filter and reabsorb approximately 180 g of glucose daily with virtually no glucose excreted in the urine. However, once the maximal limits of reabsorption are reached, the excess glucose starts to get excreted in the urine [25,51]. The SGLTs are a family of membrane proteins that are associated with the transport of glucose and ions over the brush-border membrane of proximal renal tubules and the intestinal epithelium [3].…”

“…Sodium-glucose cotransporter-2 inhibitors (SGLT2i), developed initially as a class of anti-hyperglycaemic drugs, have both glycaemic and non-glycaemic benefits. Recent advances in the understanding of the nonglycaemic effects of SGLT2i have shown cardiovascular (CV) and renal protection, with potential benefits in heart failure (HF) [23,25,40,51].…”

“…The therapeutically approach of these patients further evolved aiming at efficacy rather than just safety, treating diabetic patients with HF with drugs that improve CV outcome along with their anti-hyperglycaemic effect. The latest years have revolutionized the use of these drugs with the repurposing to treat HF, even in the absence of diabetes [23,25]. Briefly, SGLT2 inhibitors act to reduce blood glucose by blocking its reabsorption in the kidneys leading to urinary glucose excretion, reduced blood glucose levels, and reduction of plasma volume and sodium load [31].…”