In this article we have used consensus expert opinion alongside the available evidence, product indication and most recent clinical guidance to provide support for the diabetes healthcare community regarding the appropriate use of SGLT2 inhibitors, focussing on specific considerations for appropriate prescribing of dapagliflozin within the T1DM management pathway.
Whilst we have little direct evidence for the antiplatelet effects of SGLT2 inhibitors, some studies have shown that these agents may inhibit platelet aggregation and reduce the risk of thrombotic events in diabetes.
Recently SGLT2 inhibitors showed the promising result to treat diabetes and therefore several molecules are approved by US FDA Objective: SGLT2 inhibitors were designed based on the dioxabicyclo[3.2.1] octane with the aim to search new lead molecule.
The consistent observation of an increase in hematocrit, even in those without diabetes, has led to the hypothesis that SGLT2 inhibitors may increase erythropoiesis via enhanced erythropoietin (EPO) secretion by the kidney.<sup>4</sup> This SGLT2 inhibitor mediated increase in EPO production (and resultant rise in hematocrit) could lead to systemic organ protection by virtue of its capacity as a circulating pleiotropic cytokine, known to favorably influence cardiomyocyte mitochondrial function, angiogenesis, cell proliferation and inflammation.
Furthermore, the benefit of SGLT-2 inhibitors in a population of patients with HF yet without diabetes remains to be demonstrated across multiple trials.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are therapeutic agents that have been used recently to reduce tubular absorption of glucose, leading to enhanced glycosuria, resulting in the reduction of blood glucose and improved diabetes control.
<i>Sglt1</i> (also known as <i>Slc5a1</i>) and <i>Sglt2</i> (also known as <i>Slc5a2</i>) knockout mice were employed to develop sotagliflozin, a dual SGLT1/SGLT2 inhibitor having success in clinical trials for diabetes.
This review comprises a summary of patent applications (2013-2018) of SGLT2 inhibitors with focus on chemical structural advancement and therapeutic potentials in the management of diabetes and related disorders.
At the present time, SGLT2 inhibitors are indicated for the treatment of type 2 diabetes; however, the results of ongoing trials in participants with heart failure but without diabetes are eagerly awaited.
Such SGLT2 inhibitors exert favourable effects in experimental models of HFpEF and have been found in large-scale trials to reduce the risk for serious heart failure events in patients with type 2 diabetes, many of whom were retrospectively identified as having HFpEF.
The Q-Finder algorithm identified four clinically relevant subgroups showing superior RFP with SGLT2 inhibitors (P < 0.1): no hyperlipidaemia and eGFR ≥79 mL/min/1.73 m<sup>2</sup> ; eGFR ≥79 mL/min/1.73 m<sup>2</sup> and diabetes duration ≤1.2 years; eGFR ≥75 mL/min/1.73 m<sup>2</sup> and use of antithrombotic agents; and haemoglobin ≤13.4 g/dL and LDL cholesterol ≥95.1 mg/dL.
The action of SGLT2 inhibitors to promote ketogenesis is also primarily a feature of the action of these drugs in patients with diabetes, raising doubts that enhanced ketogenesis contributes to the benefit on heart failure.
We report data on the use of SGLT2 inhibitors in a case series of ten patients with diabetes after kidney transplantation in order to analyze efficacy, safety, and the effect on renal function.
In this mouse model of diabetes and NASH/HCC, canagliflozin showed anti-steatotic and anti-inflammatory effects that attenuated the development of NASH and prevented the progression of NASH to HCC, partly due to the induction of cell cycle arrest and/or apoptosis as well as the reduction of tumor growth through the direct inhibition of SGLT2 in tumor cells.
Reports that sodium glucose cotransporter 2 inhibitors decrease cardiovascular death and events in patients with diabetes have attracted attention in the cardiology field.
The EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial in patients with Type 2 Diabetes Mellitus (T2DM)) trial made evident the potentiality of pharmacological sodium-glucose cotransporter 2 (SGLT2) inhibition for treating patients with diabetes and cardiovascular disease.
In this work, aiming at finding a novel, potent, and selective sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor with good pharmacokinetic profiles for the treatment of diabetes, we focus on modifying the sugar moiety of SGLT2 inhibitors, which dominates the binding with glucose binding site of hSGLT, via removing the C-6 hydroxy group to adjust the physicochemical properties and target-recognition manners of SGLT2 inhibitors.
While dipeptidyl peptidase-4 (DPP-4) inhibitors exhibited increased heart failure hospitalization in the SAVOR-TIMI 53 trial evaluating saxagliptin and in the secondary analysis of the EXAMINE trial for alogliptin, the effects of glucagon-like peptide-1 (GLP-1) analogs and sodium-glucose co-transporter-2 (SGLT2) inhibitors on CV outcomes in diabetes have largely been positive.
These data offer a rationale for use of thiazide in individuals with diabetes and provide insights into the mechanism for cardiorenal protective effects of SGLT2 inhibitors.
These include three independent glucosuria variants at SLC5A2, the gene encoding the sodium-dependent glucose transporter (SGLT2), a protein targeted pharmacologically to increase urinary glucose excretion in the treatment of diabetes.