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.
These trials are changing the landscape of diabetes therapy with evidence beyond safety to cardiovascular benefits of sodium-glucose cotransporter 2 (SGLT-2) inhibitors and some glucagon-like peptide-1 receptor agonists.
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.
Safety and efficiency of SGLT2 inhibitor combining with insulin in subjects with diabetes: Systematic review and meta-analysis of randomized controlled trials.
Reduced renal glucose reabsorption by SGLT2 inhibition seems to have high potential to improve glycemic control in diabetes mellitus (DM) not only through glucose lowering but also through glucose-independent effects such as blood pressure-lowering and direct renal effects in 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.
We utilized this model to quantify glucose and Na reabsorption through SGLT2 in healthy, controlled, and uncontrolled diabetes and following treatment with canagliflozin.
Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects.
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.
Although the degree to which aggressive glycated hemoglobin reduction decreases the risk of macrovascular outcomes remains unclear, the use of specific agents, such as the newer sodium glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) agonists, may reduce cardiovascular events in patients with diabetes, irrespective of glycated hemoglobin reduction.
In whole renal tissue, expressions of SGLT2/GLUT2 and SGLT1/GLUT1 are coupled and slightly lower in typical people with T2DM as compared with well-matched people without diabetes.
Treatment of hyperglycemia with drugs that block renal glucose reabsorption via inhibition of sodium-dependent glucose cotransporter 2 (SGLT2) is a novel approach to diabetes management.
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.
Erratum: Safety and efficiency of SGLT2 inhibitor combining with insulin in subjects with diabetes: Systematic review and meta-analysis of randomized controlled trials: Erratum.
GLP-1 analogues and SGLT-2 inhibitors are currently approved for use in diabetes, have shown early efficacy in NASH and also have beneficial cardiovascular effects.
This review focusses on the effects of SGLT2 inhibitors on the kidney and renal outcome: it briefly outlines renal glucose handling in diabetes and its role in glomerular hyperfiltration and renal hypoxia; describes how SGLT2 inhibitors induce an early, reversible reduction in glomerular filtration rate (GFR) and preserve GFR in the long-term in patients with T2DM; discusses whether the enhanced active transport in the renal outer medulla (OM) in response to SGLT2 inhibition is friend or foe; proposes how the blood pressure lowering and heart failure protective effect of SGLT2 inhibitors can be preserved in chronic kidney disease (CKD) despite attenuated antihyperglycemic effects; and examines whether SGLT2 inhibition enhances the incidence or severity of acute kidney injury (AKI).