Mechanisms Of Sodium Glucose Cotransporter 2 Inhibitors Research Articles

SGLT2 inhibitor improves the prognosis of patients with coronary heart disease and prevents in-stent restenosis.

Coronary heart disease is a narrowing or obstruction of the vascular cavity caused by atherosclerosis of the coronary arteries, which leads to myocardial ischemia and hypoxia. At present, percutaneous coronary intervention (PCI) is an effective treatment for coronary atherosclerotic heart disease. Restenosis is the main limiting factor of the long-term success of PCI, and it is also a difficult problem in the field of intervention. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new oral glucose-lowering agent used in the treatment of diabetes in recent years. Recent studies have shown that SGLT2 inhibitors can effectively improve the prognosis of patients after PCI and reduce the occurrence of restenosis. This review provides an overview of the clinical studies and mechanisms of SGLT2 inhibitors in the prevention of restenosis, providing a new option for improving the clinical prognosis of patients after PCI.

Sodium-glucose Cotransporter 2 Inhibitors and Pathological Myocardial Hypertrophy.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new type of oral hypoglycemic drugs that exert a hypoglycemic effect by blocking the reabsorption of glucose in the proximal renal tubules, thus promoting the excretion of glucose from urine. Their hypoglycemic effect is not dependent on insulin. Increasing data shows that SGLT2 inhibitors improve cardiovascular outcomes in patients with type 2 diabetes. Previous studies have demonstrated that SGLT2 inhibitors can reduce pathological myocardial hypertrophy with or without diabetes, but the exact mechanism remains to be elucidated. To clarify the relationship between SGLT2 inhibitors and pathological myocardial hypertrophy, with a view to providing a reference for the future treatment thereof, this study reviewed the possible mechanisms of SGLT2 inhibitors in attenuating pathological myocardial hypertrophy. We focused specifically on the mechanisms in terms of inflammation, oxidative stress, myocardial fibrosis, mitochondrial function, epicardial lipids, endothelial function, insulin resistance, cardiac hydrogen and sodium exchange, and autophagy.

Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease.

Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.

Mechanisms of SGLT2 Inhibitors in Heart Failure and Their Clinical Value.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used to treat diabetes mellitus. Abundant evidence has shown that SGLT2 inhibitors can reduce hospitalization for heart failure (HF) in patients with or without diabetes. An increasing number of studies are being conducted on the mechanisms of action of SGLT2 inhibitors in HF. Our review summarizes a series of clinical trials on the cardioprotective effects of SGLT2 inhibitors in the treatment of HF. We have summarized several classical SGLT2 inhibitors in cardioprotection research, including empagliflozin, dapagliflozin, canagliflozin, ertugliflozin, and sotagliflozin. In addition, we provided a brief overview of the safety and benefits of SGLT2 inhibitors. Finally, we focused on the mechanisms of SGLT2 inhibitors in the treatment of HF, including ion-exchange regulation, volume regulation, ventricular remodeling, and cardiac energy metabolism. Exploring the mechanisms of SGLT2 inhibitors has provided insight into repurposing these diabetic drugs for the treatment of HF.

Pharmacological mechanisms of sodium-glucose co-transporter 2 inhibitors in heart failure with preserved ejection fraction

BackgroundMore and more evidence indicates sodium-glucose co-transporter 2 inhibitors (SGLT2is) may display clinical benefits for heart failure with preserved ejection fraction (HFpEF). However, the mechanisms of the action remain unclear.MethodsA systematic pharmacology-based strategy was applied for predicting the potential molecular mechanisms of SGLT2is in HFpEF. The potential targets of SGLT2is and HFpEF were contained from diverse databases. After networks were constructed, Metascape was applied to functional enrichment. Moreover, the key findings were validated through molecular docking.ResultsWe obtained 487 SGLT2is related targets and 1505 HFpEF related targets. The networks showed the complex relationship of HFpEF-target-HFpEF. The results of functional enrichment analysis suggested that several biological processes, including muscle system process, inflammatory response, vasculature development, heart development, regulation of MAPK cascade, positive regulation of ion transport, negative regulation of cell population proliferation, cellular response to nitrogen compound, apoptotic signaling pathway, multicellular organismal homeostasis, response to oxidative stress, regulation of cell adhesion, positive regulation of cell death, response to growth factor, and cellular response to lipid, and signaling pathways, such as cardiomyopathy, cAMP signaling pathway, cytokine-cytokine receptor interaction, apoptosis, MAPK signaling pathway, HIF-1 signaling pathway, calcium signaling pathway, and NF-kappa B signaling pathway. Finally, we validated the interactions and combinations of SGLT2is and core targets.ConclusionSGLT2is play the potential role of anti-HFpEF through the direct or indirect synergy of multiple targets and pathways. Our study promotes the explanation of the molecular mechanisms of SGLT2is in HFpEF.

Prevention and Management of Heart Failure: Role of SGLT2 Inhibitors in Patients With and Without Diabetes

Certain antidiabetic therapies have adverse cardiovascular (CV) consequences. The recommendations for CV safety studies for new antidiabetic therapies led to the discovery that the sodium-glucose cotransporter-2 inhibitors (SGLT2is) have benefits in heart failure (HF) management. Mounting evidence from large, international, randomized, placebo-controlled trials have consistently demonstrated a reduction in hospitalizations for heart failure (HHF) among populations with type 2 diabetes or with HF with reduced ejection fraction. In vitro, animal and human studies have attempted to identify the cardioprotective mechanisms of SGLT2is, although these are not yet clearly defined. This review will summarize the major SGLT2i trials, which have resulted in valuable additions to CV care that are expected to significantly reduce both incident HF and established HF progression.

The Role of SGLT2 Inhibitors in Atherosclerosis: A Narrative Mini-Review.

Objective: Sodium glucose cotransporter 2 inhibitors (SGLT2-is) are antidiabetic drugs that improve glycemic control by limiting urinary glucose reuptake in the proximal tubule. SGLT2-is might suppress atherosclerotic processes and ameliorate the prognosis of patients with diabetes mellitus diagnosed with or at high risk of atherosclerotic cardiovascular disease (ASCVD). In this mini review, we examine the role of SGLT2-is in the development and progression of atherosclerosis throughout its spectrum, from subclinical atherosclerosis to ASCVD. Data Sources—PubMed and Google Scholar were searched for publications related to SGLT2-is and atherosclerosis. All types of articles were considered, including clinical trials, animal studies, in vitro observations, and reviews and meta-analyses. Data were examined according to their impact and clinical relevance. Synopsis of Content—We first review the underlying mechanisms of SGLT2-is on the development and progression of atherosclerosis, including favorable effects on lipid metabolism, reduction of systemic inflammation, and improvement of endothelial function. We then discuss the putative impact of SGLT2-is on the formation, composition, and stability of atherosclerotic plaque. Furthermore, we evaluate the effects of SGLT2-is in subclinical atherosclerosis assessed by carotid intima media thickness and pulse wave velocity. Subsequently, we summarize the effects of SGLT2-is in ASCVD events, including ischemic stroke, angina pectoris, myocardial infarction, revascularization, and peripheral artery disease, as well as major adverse cardiovascular events, cardiovascular mortality, heart failure, and chronic kidney disease. Moreover, we examine factors that could modify the role of SGLT2-is in atherosclerosis, including sex, age, diabetes, glycemic control, ASCVD, and SGLT2-i compounds. Additionally, we propose future directions that can improve our understanding of SGLT2-is and atherosclerosis.

Sodium–Glucose Cotransporter-2 Inhibitors for Heart Failure: The New Kid on the Block

Sodium–glucose cotransporter-2 (SGLT2) inhibitors recently emerged as an effective therapy for heart failure (HF) with reduced ejection fraction. Recent published clinical trials have confirmed these agents substantially reduce mortality and HF hospitalization among patients with established HF with reduced ejection fraction, with or without type 2 diabetes. Ongoing studies are evaluating the effects of SGLT2 inhibitors on clinical outcomes for patients with HF with preserved ejection fraction. Nurse practitioners must understand the indications and mechanisms of SGLT2 inhibitors when prescribing. Thoughtful collaboration between cardiology and endocrine providers can guide management with the use of SGLT2 inhibitors in complicated HF patients.

Bibliometric Study of Sodium Glucose Cotransporter 2 Inhibitors in Cardiovascular Research.

BackgroundAn increasing number of studies have shown that sodium glucose cotransporter 2 (SGLT2) inhibitors, initially used as antidiabetic agents, have cardiovascular (CV) benefits. However, few bibliometric analyses have examined this field systematically. Our study aimed to visualize the publications to determine the trends and hotspots in CV research on SGLT2 inhibitors.MethodsPublications on SGLT2 inhibitors in cardiovascular research were retrieved from the Web of Science Core Collection. Microsoft Excel 2019, VOSviewer, and CiteSpace V were used to analyze and plot the references.ResultsOn July 3, 2020, 1509 records of CV research on SGLT2 inhibitors published from 2013 to 2020 were retrieved. Nearly half were authored by American scholars, and most were published in Diabetes Obesity Metabolism, Cardiovascular Diabetology, and Diabetes Therapy. The USA was the leading driving force, with a strong academic reputation in this area. Inzucchi SE published the most related articles, while Neal B was cited the most frequently. All the top 10 co-cited references were in the leading co-cited journal, The New England Journal of Medicine. “Atherosclerotic cardiovascular event” was the leading research hotspot. The keywords “cardiac metabolism,” “heart failure hospitalization,” and “heart failure with preserved ejection fraction” appeared most recently as research frontiers.ConclusionMost studies focused on clinical trial outcomes, such as cardiovascular death and heart failure (HF) hospitalization. The mechanisms of SGLT2 inhibitors, especially those related to cardiac metabolism, may soon become hotspots and should be closely monitored.

P4466Empagliflozin improves heart function after myocardial infarction in the rat

Abstract Background Selective Sodium-glucose cotransporter 2 (SGLT2) inhibition with Empagliflozin reduced progression of left ventricular dysfunction and improved tolerance of physical exercise in heart failure by normoglycemic rats. Here, we hypothesized that Empagliflozin prevents cardiac dysfunction after myocardial infarction (MI). Purpose This study aimed to investigate whether Empagliflozin protects the heart in the early phase after experimental MI in normoglycemic rats. Methods MI was induced in Wistar rats via permanent ligation of the left coronary artery. Treatment with Empagliflozin (1 mg/kg/daily per os) was started after MI and continued for 7 days. Sham operated and vehicle treated animals served as controls (n=8). Hemodynamic parameters were measured via transthoracic echocardiography and intracardiac Samba catheter. Glucose concentration was determined in serum and urine. Protein expression of Na+/H+ exchanger isoform-1 (NHE-1), sodium bicarbonate co-transporter (NBC), Sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), transforming growth factor beta 1 (TGF-beta1), Smad2 in the left ventricle were also studied. Additionally, NHE-1 regulation was investigated in cardiomyocyte cell line H9c2. Results Systolic heart function was improved in Empagliflozin treated MI animals compared to vehicle as demonstrated by Global Longitudinal Strain (GLS) (20,9% vs. 16,6%; p<0.05). E/A ratio was decreased by tendency and blood pressure was not affected. Ejection fraction (p<0.05), fractional shortening (p<0.05), stroke volume (p<0.01) were increased in Empagliflozin treated control rats as compared with the sham group. Moreover, application of Empagliflozin (1mg/kg, i.v. bolus) to healthy rats in 30 min increased maximal pressure in the left ventricle as compared with vehicle (110,5±15,3 mmHg vs 79,1±11,9 mmHg; p<0.05). Parallel, dP/dtmax was increased while dP/dtmin was decreased by tendency. Empagliflozin treatment did not affect glucose concentration in serum and urine. Treatment of cardiac H9c2 cells with Empagliflozin (1μM) down-regulated NHE-1 by 27%. Conclusion SGLT2 inhibitor Empagliflozin improved systolic function in the early phase post MI independently from glucose regulation. The cardioprotective mechanisms of SGLT2 inhibitors may involve cardiac NHE-1 exchanger inhibition.