scholarly journals The expanding role of SGLT2 inhibitors beyond glucose-lowering to cardiorenal protection

2020 ◽  
pp. 1-32
Author(s):  
Emily Brown ◽  
John PH Wilding ◽  
Uazman Alam ◽  
Thomas M Barber ◽  
Janaka Karalliedde ◽  
...  
Keyword(s):  
Sglt2 Inhibitors ◽  
Glucose Lowering

scholarly journals Sodium–Glucose Cotransporter-2 Inhibitors and Heart Failure Prevention in Type 2 Diabetes

2019 ◽  
Vol 5 (3) ◽  
pp. 169-172 ◽  
Author(s):  
Muhammad Shahzeb Khan ◽  
Javed Butler
Keyword(s):  
Heart Failure ◽  
Sglt2 Inhibitors ◽  
Current Evidence ◽  
Future Directions ◽  
Glucose Lowering ◽  
Sodium Glucose Cotransporter ◽  
Reduce Risk ◽  
Worse Prognosis

Diabetes and heart failure (HF) are closely linked, with one causing a worse prognosis in the other. The majority of anti-hyperglycaemic agents primarily reduce risk of ischaemic microvascular events without targeting the mechanisms involved for diabetes cardiomyopathy and HF. Sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as a novel class of glucose-lowering agents that have consistently reduced HF hospitalisations, unlike other agents. The authors discuss the current evidence and highlight possible future directions for the role of SGLT2 inhibitors in HF prevention.

scholarly journals The Na/K-ATPase Signaling and SGLT2 Inhibitor-Mediated Cardiorenal Protection: A Crossed Road?

2021 ◽  
Author(s):  
Jiang Liu ◽  
Jiang Tian ◽  
Komal Sodhi ◽  
Joseph I. Shapiro
Keyword(s):  
Large Scale ◽  
Sglt2 Inhibitor ◽  
Sglt2 Inhibitors ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Sodium Potassium ◽  
Glucose Lowering ◽  
Ion Transporter ◽  
Signaling Function

AbstractIn different large-scale clinic outcome trials, sodium (Na+)/glucose co-transporter 2 (SGLT2) inhibitors showed profound cardiac- and renal-protective effects, making them revolutionary treatments for heart failure and kidney disease. Different theories are proposed according to the emerging protective effects other than the original purpose of glucose-lowering in diabetic patients. As the ATP-dependent primary ion transporter providing the Na+ gradient to drive other Na+-dependent transporters, the possible role of the sodium–potassium adenosine triphosphatase (Na/K-ATPase) as the primary ion transporter and its signaling function is not explored. Graphic Abstract

scholarly journals Emergence of SGLT2 Inhibitors as Powerful Antioxidants in Human Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1166
Author(s):  
Kai-Fan Tsai ◽  
Yung-Lung Chen ◽  
Terry Ting-Yu Chiou ◽  
Tian-Huei Chu ◽  
Lung-Chih Li ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Redox Homeostasis ◽  
Sglt2 Inhibitors ◽  
Human Diseases ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Protective Effects ◽  
Glucose Lowering ◽  
Therapeutic Benefits ◽  
Neural Disorders

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral glucose-lowering agents. Apart from their glucose-lowering effects, large clinical trials assessing certain SGLT2 inhibitors have revealed cardiac and renal protective effects in non-diabetic patients. These excellent outcomes motivated scientists and clinical professionals to revisit their underlying mechanisms. In addition to the heart and kidney, redox homeostasis is crucial in several human diseases, including liver diseases, neural disorders, and cancers, with accumulating preclinical studies demonstrating the therapeutic benefits of SGLT2 inhibitors. In the present review, we aimed to update recent advances in the antioxidant roles of SGLT2 inhibitors in common but debilitating human diseases. We anticipate that this review will guide new research directions and novel therapeutic strategies for diabetes, cardiovascular diseases, nephropathies, liver diseases, neural disorders, and cancers in the era of SGLT2 inhibitors.

scholarly journals Role of Glucose-Lowering Medications in Erectile Dysfunction

2021 ◽  
Vol 10 (11) ◽  
pp. 2501
Author(s):  
Angelo Cignarelli ◽  
Valentina Annamaria Genchi ◽  
Rossella D’Oria ◽  
Fiorella Giordano ◽  
Irene Caruso ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Current Knowledge ◽  
Smooth Muscle Contractility ◽  
Glucose Lowering ◽  
Glycation End Products ◽  
Altered Metabolism

Erectile dysfunction (ED) is a long-term complication of type 2 diabetes (T2D) widely known to affect the quality of life. Several aspects of altered metabolism in individuals with T2D may help to compromise the penile vasculature structure and functions, thus exacerbating the imbalance between smooth muscle contractility and relaxation. Among these, advanced glycation end-products and reactive oxygen species derived from a hyperglycaemic state are known to accelerate endothelial dysfunction by lowering nitric oxide bioavailability, the essential stimulus of relaxation. Although several studies have explained the pathogenetic mechanisms involved in the generation of erectile failure, few studies to date have described the efficacy of glucose-lowering medications in the restoration of normal sexual activity. Herein, we will present current knowledge about the main starters of the pathophysiology of diabetic ED and explore the role of different anti-diabetes therapies in the potential remission of ED, highlighting specific pathways whose activation or inhibition could be fundamental for sexual care in a diabetes setting.

scholarly journals Role of Melanocortin Signaling in Neuroendocrine and Metabolic Actions of Leptin in Male Rats With Uncontrolled Diabetes

Endocrinology ◽  
2014 ◽  
Vol 155 (11) ◽  
pp. 4157-4167 ◽  
Author(s):  
Thomas H. Meek ◽  
Miles E. Matsen ◽  
Vincent Damian ◽  
Alex Cubelo ◽  
Streamson C. Chua ◽  
...  
Keyword(s):  
Male Rats ◽  
Melanocortin Receptor ◽  
Glucose Lowering ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Uncontrolled Diabetes ◽  
Streptozotocin Induced Diabetes ◽  
Melanocortin Signaling ◽  
Antidiabetic Effects

Abstract Although the antidiabetic effects of leptin require intact neuronal melanocortin signaling in rodents with uncontrolled diabetes (uDM), increased melanocortin signaling is not sufficient to mimic leptin's glucose-lowering effects. The current studies were undertaken to clarify the role of melanocortin signaling in leptin's ability to correct metabolic and neuroendocrine disturbances associated with uDM. To accomplish this, bilateral cannulae were implanted in the lateral ventricle of rats with streptozotocin-induced diabetes, and leptin was coinfused with varying doses of the melanocortin 3/4 receptor (MC3/4R) antagonist, SHU9119. An additional cohort of streptozotocin-induced diabetes rats received intracerebroventricular administration of either the MC3/4R agonist, melanotan-II, or its vehicle. Consistent with previous findings, leptin's glucose-lowering effects were blocked by intracerebroventricular SHU9119. In contrast, leptin-mediated suppression of hyperglucagonemia involves both melanocortin dependent and independent mechanisms, and the degree of glucagon inhibition was associated with reduced plasma ketone body levels. Increased central nervous system melanocortin signaling alone fails to mimic leptin's ability to correct any of the metabolic or neuroendocrine disturbances associated with uDM. Moreover, the inability of increased melanocortin signaling to lower diabetic hyperglycemia does not appear to be secondary to release of the endogenous MC3/4R inverse agonist, Agouti-related peptide (AgRP), because AgRP knockout mice did not show increased susceptibility to the antidiabetic effects of increased MC3/4R signaling. Overall, these data suggest that 1) AgRP is not a major driver of diabetic hyperglycemia, 2) mechanisms independent of melanocortin signaling contribute to leptin's antidiabetic effects, and 3) melanocortin receptor blockade dissociates leptin's glucose-lowering effect from its action on other features of uDM, including reversal of hyperglucagonemia and ketosis, suggesting that brain control of ketosis, but not blood glucose levels, is glucagon dependent.

New Therapeutic Horizons in Chronic Kidney Disease: The Role of SGLT2 Inhibitors in Clinical Practice

Drugs ◽  
2021 ◽  
Author(s):  
Marc Evans ◽  
Angharad R. Morgan ◽  
Martin B. Whyte ◽  
Wasim Hanif ◽  
Stephen C. Bain ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Practice ◽  
Kidney Disease ◽  
Sglt2 Inhibitors

scholarly journals Network Meta-Analysis of Novel Glucose-Lowering Drugs on Risk of Acute Kidney Injury

2020 ◽  
Vol 16 (1) ◽  
pp. 70-78 ◽  
Author(s):  
Min Zhao ◽  
Shusen Sun ◽  
Zhenguang Huang ◽  
Tiansheng Wang ◽  
Huilin Tang
Keyword(s):  
Type 2 Diabetes ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Lower Risk ◽  
Meta Analysis ◽  
Secondary Analysis ◽  
Sglt2 Inhibitors ◽  
Glucose Lowering ◽  
Event Driven

Background and objectivesLittle is known about the comparative effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), or sodium glucose cotransporter-2 (SGLT2) inhibitors on risk of AKI. This study aimed to compare the effects of these three novel classes of glucose-lowering drugs on AKI risk in patients with or without type 2 diabetes, by network meta-analysis of event-driven cardiovascular or kidney outcome trials.Design, setting, participants, & measurementsWe systematically searched electronic databases up to September 2020, and included 20 event-driven cardiovascular or kidney outcome trials (18 trials included patients with type 2 diabetes only, and two trials included patients with or without type 2 diabetes). A network meta-analysis using a frequentist approach was performed to compare the effects of DPP-4 inhibitors, GLP-1RAs, or SGLT2 inhibitors on risk of AKI, and estimate the probability for each intervention as the safest one. The primary analysis included 18 trials with type 2 diabetes only, and a secondary analysis included 20 trials.ResultsIn the 18 trials with a total of 2051 AKI events (range: 1–300) among 156,690 patients with type 2 diabetes only, our network meta-analysis showed that SGLT2 inhibitors were associated with a lower risk of AKI compared with placebo (odds ratio, 0.76; 95% confidence interval, 0.66 to 0.88), whereas both DPP-4 inhibitors and GLP-1RAs had neutral effects on risk of AKI. Moreover, SGLT2 inhibitors were significantly associated with a lower risk in AKI than both GLP-1RAs (odds ratio, 0.79; 95% confidence interval, 0.65 to 0.97) and DPP-4 inhibitors (odds ratio, 0.68; 95% confidence interval, 0.54 to 0.86). SGLT2 inhibitors have the highest probability of being the safest intervention (84%). The results were similar in the secondary analysis.ConclusionsCurrent evidence indicates that SGLT2 inhibitors have a lower risk of AKI than both DPP-4 inhibitors and GLP-1RAs.

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