scholarly journals Cardioprotective mechanisms of sodium-glucose cotransporter 2 inhibitors

2021 ◽  
Vol 24 (3) ◽  
pp. 291-299
Author(s):  
A. M. Mkrtumyan ◽  
T. N. Markova ◽  
N. K. Mishchenko
Keyword(s):  
Large Scale ◽  
Troponin I ◽  
Ketone Bodies ◽  
Cardiovascular Effects ◽  
Metabolic Effects ◽  
Atp Production ◽  
Cardiovascular Outcome Trials ◽  
Sodium Glucose Cotransporter ◽  
Myocardial Energetics ◽  
Highly Sensitive Troponin

The findings of large-scale cardiovascular outcome trials have been demonstrated that sodium-glucose cotransporter 2 ­inhibitors (iSGLT-2) have shown beneficial cardiovascular effects. In this review proposed mechanisms underlying iSGLT-2-associated cardiovascular benefits have been discussed: haemodynamic and intracellular effects, including metabolic effects and electrolyte changes; and also, the effect on markers of cardiovascular disease (CVD). The hemodynamic effects of SGLT-2 are characterized by reduction of cardiac preload and afterload as a result of osmotic diuresis, a decrease in blood pressure and arterial stiffness. The metabolic effects of this medicine are accompanied by an increase the production of ketone bodies, followed by improving ATP production and myocardial energetics. Also, iSGLT-2 modulate ion transporters (NHE1 and NHE3). A reduction of cytoplasmic sodium and calcium levels and increasing mitochondrial calcium levels in the cardiomyocytes enhances the synthesis of ATP and increases cell viability. Effect of iSGLT-2 on CVD markers showed a decrease in the levels of the N-terminal pro-B-type natriuretic peptide and highly sensitive troponin I in elderly patients with type 2 diabetes mellitus (T2DM). Thus, this class of agents has a multifactorial effect on the functioning of cardiovascular system. Further studies will help to explain the all possible cardioprotective effects of iSGLT-2 in individuals with and without T2DM.

scholarly journals Emerging glucose-lowering therapies: a guide for cardiologists

Heart ◽  
2019 ◽  
Vol 106 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Gaurav S Gulsin ◽  
Matthew P M Graham-Brown ◽  
Melanie J Davies ◽  
Gerry P McCann
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Practice ◽  
Large Scale ◽  
Cardiovascular Outcome ◽  
Glucose Lowering ◽  
Cardiovascular Outcome Trials ◽  
Sodium Glucose Cotransporter ◽  
Emerging Treatments ◽  
Glucagon Like Peptide 1 ◽  
Safety Considerations

In recent large-scale cardiovascular outcome trials, two new classes of glucose-lowering medications—sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs)—demonstrated cardiovascular benefits in adults with type 2 diabetes mellitus (T2DM). These findings have prompted growing optimism among clinicians regarding the potential for these agents to reduce the burden of cardiovascular disease in people with T2DM. GLP-1RAs and SGLT2i are now advocated as second-line agents in European and US guidelines for management of both hyperglycaemia and for primary prevention of cardiovascular disease in people with T2DM. Given the high prevalence of T2DM in patients with cardiovascular disease, cardiologists will increasingly encounter these agents in routine clinical practice. In this review, we summarise evidence from cardiovascular outcome trials of GLP-1RAs and SGLT2i, give practical advice on prescribing and detail safety considerations associated with their use. We also highlight areas where further work is needed, giving details on active clinical trials. The review aims to familiarise cardiologists with these emerging treatments, which will be increasingly encountered in clinical practice, given the expanding representation of T2DM in patients with cardiovascular disease. Whether these drugs will be initiated by cardiologists remains to be determined.

Cardio-protective effects of sodium-glucose co-transporter 2 inhibitors: focus on heart failure

2020 ◽  
Vol 26 ◽  
Author(s):  
Dimos Karangelis ◽  
C. David Mazer ◽  
Dimitrios Stakos ◽  
Aphrodite Tzifa ◽  
Spiros Loggos ◽  
...  
Keyword(s):  
Heart Failure ◽  
Large Scale ◽  
Mechanisms Of Action ◽  
Sglt2 Inhibitors ◽  
Protective Effects ◽  
Reduced Ejection Fraction ◽  
Risk Of Death ◽  
Sodium Glucose Cotransporter ◽  
Myocardial Energetics

Background: Type 2 diabetes mellitus (DM) is associated with a considerable risk of cardiovascular and renal disease, including heart failure. Sodium–glucose cotransporter 2 (SGLT2) inhibitors have demonstrated unprecedented cardiorenal protective effects in large scale clinical trials of patients with or without diabetes and either established cardiovascular disease (CV) or multiple CV risk factors. Objective: Herein we aim to focus on the role of SGLT2 inhibitors regarding the improvement in heart failure outcomes and the proposed mechanisms of action by which these drugs confer their beneficial effect. Methods: PubMed, Embase and Google Scholar databases were searched to identify eligible articles which are comprehensively summarized and discussed. Results: The most commonly discussed mechanisms of action are diuresis and natriuresis, reduction in preload, afterload, and ventricular mass, as well as stimulation of erythropoietin production and improved myocardial energetics. SGLT2 inhibitors improve outcomes in patients with established heart failure (HF) and reduce the risk of death and HF admissions in patients with established chronic HF with reduced ejection fraction (HFrEF), either with or without diabetes. Conclusion: Potential key mechanisms that may explain the notable cardioprotective benefits of SGLT2 inhibitors have been outlined. These agents have recently received class Ia recommendation in specific groups of people with DM to lower the risk of hospitalization for HF and risk of death, while these benefits may also extend to people without diabetes. It remains to be seen whether they will also emerge as treatment approaches in the acute phase of CV episodes.

scholarly journals Non Incretin Effects of DPP-4 Inhibitors: Comparative Study

2019 ◽  
Vol 1 (1) ◽  
pp. 8-12
Author(s):  
A Shabbir Ali Bhatti ◽  
Aliya Shabbir ◽  
Abdul Waheed Shehzad ◽  
M. A.Bhatti
Keyword(s):  
Coronary Flow ◽  
Cardiovascular Effects ◽  
Experimental Models ◽  
The Body ◽  
Metabolic Effects ◽  
Inotropic Effects ◽  
Multifunctional Protein ◽  
Dipeptidyl Peptidase 4 ◽  
Cardiovascular Outcome Trials ◽  
Experimental Drugs

Background: Diabetes mellitus is a metabolic syndrome that adversely affects all parts of the body especially the cardiovascular system. Dipeptidyl peptidase-4 (DPP-4) is a multifunctional protein and its inhibition has diverse effects. DPP-4 inhibition was shown to improve the survival rate after myocardial infarction in mice. Beneficial myocardial metabolic effects of DPP-4 inhibitors have been observed in experimental models. Cardiovascular outcome trials of DPP-4 inhibitors show variable adverse cardiovascular events. Objective: This experimental study was aimed to study the direct cardiovascular effects of DPP-4 Inhibitors on chronotropicity (Heart Rate, HR), inotropicity (Apical Force and; dP/dt(max), ECG and Coronary Flow(C.F) and detect its potential useful and harmful effects on cardiovascular parameters. Methods: The effects of graded doses (10-9 - 10-6M) of Sitagliptin (S) and Vildagliptin(V) were observed on retrograde perfused isolated rabbit hearts with warm Krebs-Henseliet solution on Radnoti working heart system. Fifty four(54) rabbits were grouped into nine groups i.e ; I(S1), II(S2), III(S3), IV(S4), V(S5), VI(S6), VII(V1), and VIII(V2) and IX(V3) each comprising of six animals(n=6).Effects of experimental drugs were observed on chronotropicity(HR), inotropicity (Apical Force and Peak rate of rise of LVP i.e; dP/dt(max) and Coronary flow(CF). The results were statistically analyzed with Graph Pad Grism and wherever necessary paired or unpaired “t” test was applied. Conclusion: Sitagliptin and Vildagliptin both have suppressant effects on HR. Sitagliptin has positive and Vildagliptin had negative inotropic effects. Both drugs (10-8 - 10-6M); decrease coronary flow but have no significant effect on ECG.

scholarly journals Sodium-Glucose Cotransporter-2 Inhibitors in Patients with Hereditary Podocytopathies, Alport Syndrome, and FSGS: A Case Series to Better Plan a Large-Scale Study

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1815
Author(s):  
Jan Boeckhaus ◽  
Oliver Gross
Keyword(s):  
Glomerular Filtration ◽  
Alport Syndrome ◽  
Large Scale ◽  
Case Series ◽  
Hereditary Diseases ◽  
Glomerular Filtration Barrier ◽  
Early Effect ◽  
Filtration Barrier ◽  
First Case ◽  
Sodium Glucose Cotransporter

Hereditary diseases of the glomerular filtration barrier are characterized by a more vulnerable glomerular basement membrane and dysfunctional podocytes. Recent clinical trials have demonstrated the nephroprotective effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in chronic kidney disease (CKD). SGLT2-mediated afferent arteriole vasoconstriction is hypothesized to correct the hemodynamic overload of the glomerular filtration barrier in hereditary podocytopathies. To test this hypothesis, we report data in a case series of patients with Alport syndrome and focal segmental glomerulosclerosis (FSGS) with respect of the early effect of SGLT2i on the kidney function. Mean duration of treatment was 4.5 (±2.9) months. Mean serum creatinine before and after SGLT-2i initiation was 1.46 (±0.42) and 1.58 (±0.55) mg/dL, respectively, with a median estimated glomerular filtration rate of 64 (±27) before and 64 (±32) mL/min/1.73 m2 after initiation of SGLT2i. Mean urinary albumin-creatinine ratio in mg/g creatinine before SGLT-2i initiation was 1827 (±1560) and decreased by almost 40% to 1127 (±854) after SGLT2i initiation. To our knowledge, this is the first case series on the effect and safety of SGLT2i in patients with hereditary podocytopathies. Specific large-scale trials in podocytopathies are needed to confirm our findings in this population with a tremendous unmet medical need for more effective, early on, and safe nephroprotective therapies.

The Removal of Infused Leucine after Injury, Starvation and other Conditions in Man

1980 ◽  
Vol 59 (4) ◽  
pp. 275-283 ◽  
Author(s):  
M. Elia ◽  
Rose Farrell ◽  
Vera Ilic ◽  
R. Smith ◽  
D. H. Williamson
Keyword(s):  
Muscular Dystrophy ◽  
Blood Concentration ◽  
Ketone Bodies ◽  
Elective Surgery ◽  
Metabolic Effects ◽  
Accidental Injury ◽  
Sufficient Energy ◽  
Branched Chain ◽  
Clinical Conditions ◽  
Basal Concentration

1. To investigate the effects of starvation, elective surgery, accidental injury and other clinical conditions on the metabolism of branched-chain amino acids in man, we have measured the basal concentration of leucine and the removal and metabolic effects of infused l-leucine. 2. The blood concentration of leucine was significantly increased by surgery, starvation and accidental injury, and decreased in cirrhosis. It tended to increase in diabetes and was unaffected by muscular dystrophy. 3. The half-life of infused leucine was nearly doubled by 4 days of complete starvation, unaltered by surgery and decreased by severe accidental injury. Infusion with Intralipid, which increased free fatty acid and ketone-body concentrations, had no effect on the removal of a leucine load. The clearance rate of infused leucine was reduced in diabetes and muscular dystrophy and increased in cirrhosis. 4. The effects of infused leucine on blood glucose and ketone bodies differed according to the groups studied. 5. Since the traumatized patients were given sufficient energy and nitrogen and disposed of a leucine load at a different rate from the starved patients, the causes of the increase in blood concentration of leucine in these two conditions are different.

scholarly journals The Influence of Regular Hemodialysis on the Highly Sensitive Troponin-I Level in Children without Any Symptoms

2021 ◽  
Vol 11 (02) ◽  
pp. 183-198
Author(s):  
Hekmat Mohamed ◽  
Maha Youssef ◽  
Manal Abdel-Salam ◽  
Shayma A. Mohammed
Keyword(s):  
Troponin I ◽  
Highly Sensitive ◽  
Highly Sensitive Troponin ◽  
Regular Hemodialysis

scholarly journals How should we monitor the cardiovascular benefit of sodium–glucose cotransporter 2 inhibition?

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Koichi Node
Keyword(s):  
Sglt2 Inhibitor ◽  
Cardiovascular Outcomes ◽  
Sglt2 Inhibitors ◽  
Inhibitor Therapy ◽  
Cardiovascular Outcome ◽  
Cardiovascular Outcome Trials ◽  
Amino Terminal ◽  
Sodium Glucose Cotransporter ◽  
Diabetes Status ◽  
Cardiovascular Benefit

AbstractSodium–glucose cotransporter 2 (SGLT2) inhibitors are increasingly prescribed for the treatment of patients with type 2 diabetes to reduce the risk of cardiovascular events, including heart failure (HF). The mechanisms by which SGLT2 inhibitors reduce such risk are likely to be independent of diabetes status and improvement of glycemic control. In this commentary, based on recent mediation analyses of cardiovascular outcome trials with SGLT2 inhibitors, we discuss the prognostic role of a well-known HF-related biomarker, amino-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients receiving SGLT2 inhibitors. Interestingly, the NT-proBNP concentration had a relatively small impact on the SGLT2 inhibitor-associated benefit on HF events, suggesting a limited value in measuring NT-proBNP concentrations to monitor effects on cardiovascular outcomes after initiation of SGLT2 inhibitor therapy. Instead, clinical factors, such as body weight and volume status, were prognostic for cardiovascular outcomes. As shown in some biomarker studies, short-term SGLT2 inhibitor treatment significantly improved volume and HF-related health status, despite the absence of a significant change in NT-proBNP concentration. Given the early and continuous risk reduction in HF events seen in the cardiovascular outcome trials with SGLT2 inhibitors, changes in these fundamental clinical parameters after initiation of SGLT2 inhibitor therapy, independent of NT-proBNP, could be more prognostic and could represent key determinants to identify responders or non-responders to SGLT2 inhibitors for cardiovascular outcomes. Thus, this commentary highlights the clinical importance of establishing how clinicians should monitor patients initiating SGLT2 inhibitor therapy to predict the expected cardiovascular benefit. Further detailed investigations and discussion to better understand this ‘‘black box’’ are urgently warranted.

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