scholarly journals Sodium-Glucose Cotransporter-2 Inhibitors and Cardiovascular Disease: Lessons and the Future

2020 ◽  
Vol 4 (1) ◽  
pp. 10-12
Author(s):  
Abdulhalim J. A. Kinsara ◽  
◽  
Atif Al Qubbany ◽  
Wail Alkashkar ◽  
◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Communicable Disease ◽  
Therapeutic Option ◽  
Vascular Complications ◽  
Cardiovascular Complications ◽  
Diabetic Patients ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Related Hospitalisation

Diabetes mellitus (DM), an epidemic non-communicable disease, is associated with macro- and micro-vascular complications which may result in sudden cardiac death at a young age. Sodium-glucose cotransporter-2 inhibitors (SGLT2-I) emerged as a new therapeutic option for managing DM with cardiovascular complications as well as diabetic patients with multiple risk factors. Three drugs in this class significantly reduced cardiovascular mortality and heart failure events, in both type 2 diabetes mellitus and non-diabetic patients with a reduced ejection fraction, to prevent heart failure-related hospitalisation. Evidence of kidney protection was another major advantage provided in more than one study. We reviewed recent SGLT2-I related literature and discuss the benefits beyond the cardiac system.

P777Changes in glycated hemoglobin in patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V Stassinos ◽  
S Bezati ◽  
D Leftheriotis ◽  
C Kardamis ◽  
P Dourvas ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Repeated Measures ◽  
Glycated Hemoglobin ◽  
Relative Reduction ◽  
Diabetic Patients ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure ◽  
Hba1c Levels

Abstract Introduction Glycemic control reflected by glycated hemoglobin (HbA1c) is regarded as a risk factor and a strong predictor of mortality in patients with heart failure (HF). Hyperglycemia may contribute to oxidative stress, endotelial dysfunction and cardiac fibrosis and influence negatively heart failure prognosis in patients with or without diabetes. Treatment with neprilysin inhibitors in combination with angiotensin II receptor antagonist,(ARNIs) has shown beneficial effects in morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF). Purpose We sought to investigate eventual reductions in HbA1c in patients receiving the novel therapy. Methods We enrolled a total of 52 stable patients with HFrEF eligible for treatment with ARNIs. Patients were administered a target dose of 200mg bid (97mg sacubitril/103mg valsartan) and we measured HbA1c before, 3months and 6months after initiation of therapy. Changes in HbA1c levels were tested with General Linear Model Repeated Measures test. Spearmans' Rho correlation analysis was performed to investigate possible relationship between the above. Results Mean age was 62±10 years, 69,2% of patients were on New York Heart Association (NYHA) functional class II, 23,1% on NYHA III and 7,7% on NYHA IV. 57,7% had ischemic while 42,3% dilated cardiomyopathy, 25% chronic kidney disease and 38,5% diabetes mellitus. Mean Body Mass Index (BMI) was 29,88±4,66 kg/m2. Median value of baseline HbA1c was 5,8% (IQR 0,9). Compared to baseline values, HbA1c decreased to 5,6 (IQR 0,9) and 5,7 (IQR 0,83) (p=0,012) at three and six months of treatment, respectively. Change in HbA1c levels was associated significantly with the presence of diabetes mellitus (p=0,013) and diabetic patients showed greater relative reduction in HbA1c (8%) compared to non diabetic patients (1%). Spearmans' Rho test revealed statistically significant association between changes in HbA1c levels from initiation to three months of therapy, while changes between initiation to six months of administration did non correlate with the presence of diabetes. Changes in HbA1c Conclusions HbA1c levels were reduced significantly during treatment with sacubitril/valsartan. Changes were independent of diabetes in six months of treatment.

Sodium-Glucose Cotransporter 2 Inhibitors in Heart Failure

2021 ◽  
Vol 62 (1) ◽  
Author(s):  
Kevin S. Shah ◽  
James C. Fang
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Blood Glucose Control ◽  
Sglt2 Inhibitors ◽  
Annual Review ◽  
Diabetic Patients ◽  
Publication Date ◽  
Cardiovascular Outcome Trials ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter

Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve blood glucose control by blocking renal glucose reabsorption with little subsequent risk of hypoglycemia. Consequently, there are decreases in plasma volume, body weight, and blood pressure. Additional putative benefits include improved cardiovascular energetics, decreased systemic inflammation, and less renal dysfunction. Multiple cardiovascular outcome trials in diabetic patients have demonstrated this drug class reduces the risk of adverse cardiovascular events. Reductions in heart failure (HF) hospitalization suggested that SGLT2 inhibitors might prove useful for the primary treatment of HF. Two large subsequent trials studying SGLT2 inhibitors in heart failure with reduced ejection fraction (HFrEF) demonstrated a reduction in cardiovascular mortality, HF hospitalizations, and renal-specific adverse events. This medication class is now recognized as a new pillar of therapy for patients with HFrEF. The cardiovascular and HF community await the results of ongoing trials of SGLT2 inhibition in patients with HF with preserved ejection fraction. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

scholarly journals Effect of sodium–glucose cotransporter 2 inhibitors on cardiac structure and function in type 2 diabetes mellitus patients with or without chronic heart failure: a meta-analysis

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Yi-Wen Yu ◽  
Xue-Mei Zhao ◽  
Yun-Hong Wang ◽  
Qiong Zhou ◽  
Yan Huang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Volume Index ◽  
Cardiac Structure ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter

Abstract Background Although the benefits of sodium–glucose cotransporter 2 inhibitors (SGLT2i) on cardiovascular events have been reported in patients with type 2 diabetes mellitus (T2DM) with or without heart failure (HF), the impact of SGLT2i on cardiac remodelling remains to be established. Methods We searched the PubMed, Embase, Cochrane Library and Web of Science databases up to November 16th, 2020, for randomized controlled trials reporting the effects of SGLT2i on parameters of cardiac structure, cardiac function, plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) level or the Kansas City Cardiomyopathy Questionnaire (KCCQ) score in T2DM patients with or without chronic HF. The effect size was expressed as the mean difference (MD) or standardized mean difference (SMD) and its 95% confidence interval (CI). Subgroup analyses were performed based on the stage A–B or stage C HF population and HF types. Results Compared to placebo or other antidiabetic drugs, SGLT2i showed no significant effects on left ventricular mass index, left ventricular end diastolic volume index, left ventricular end systolic volume index, or left atrial volume index. SGLT2i improved left ventricular ejection fraction only in the subgroup of HF patients with reduced ejection fraction (MD 3.16%, 95% CI 0.11 to 6.22, p = 0.04; I2 = 0%), and did not affect the global longitudinal strain in the overall analysis including stage A–B HF patients. SGLT2i showed benefits in the E/e’ ratio (MD − 0.45, 95% CI − 0.88 to − 0.03, p = 0.04; I2 = 0%), plasma NT-proBNP level (SMD − 0.09, 95% CI − 0.16 to − 0.03, p = 0.004; I2 = 0%), and the KCCQ score (SMD 3.12, 95% CI 0.76 to 5.47, p  = 0.01; I2 = 0%) in the overall population. Conclusion The use of SGLT2i was associated with significant improvements in cardiac diastolic function, plasma NT-proBNP level, and the KCCQ score in T2DM patients with or without chronic HF, but did not significantly affect cardiac structural parameters indexed by body surface area. The LVEF level was improved only in HF patients with reduced ejection fraction.

Mechanisms underlying heart failure in type 2 diabetes mellitus

2019 ◽  
pp. 37-39
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Experimental Studies ◽  
Vascular Complications ◽  
Molecular Alterations ◽  
Increased Risk ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Cardio Vascular

The prevalence of heart failure is markedly increased in individuals with diabetes mellitus. Numerous observational studies suggest that this increased risk for heart failure can be attributed to exacerbated vascular complications and the presence of increased risk factors in diabetic subjects. In addition, experimental studies revealed the presence of a number of distinct molecular alterations in the myocardium that occur independently of vascular disease and hypertension. Many of these molecular alterations are similarly observed in failing hearts of nondiabetic patients and have thus been proposed to contribute to the increased risk for heart failure in diabetes. The interest in understanding the underlying mechanisms of impaired cardio- vascular outcomes in diabetic individuals has much increased since the demonstration of cardioprotective effects of SGLT-2 inhibitors and GLP-1 receptor agonists in recent clinical trials. The current review therefore summarizes the distinct mechanisms that have been proposed to increase the risk for heart failure in diabetes mellitus.

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

scholarly journals Heart Failure and Diabetes Mellitus: Biomarkers in Risk Stratification and Prognostication

2021 ◽  
Vol 11 (10) ◽  
pp. 4397
Author(s):  
Michael Lichtenauer ◽  
Peter Jirak ◽  
Vera Paar ◽  
Brigitte Sipos ◽  
Kristen Kopp ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Risk Stratification ◽  
Natriuretic Peptides ◽  
Predictive Ability ◽  
High Sensitivity ◽  
Routine Practice ◽  
Reduced Ejection Fraction ◽  
Novel Biomarkers

Heart failure (HF) and type 2 diabetes mellitus (T2DM) have a synergistic effect on cardiovascular (CV) morbidity and mortality in patients with established CV disease (CVD). The aim of this review is to summarize the knowledge regarding the discriminative abilities of conventional and novel biomarkers in T2DM patients with established HF or at higher risk of developing HF. While conventional biomarkers, such as natriuretic peptides and high-sensitivity troponins demonstrate high predictive ability in HF with reduced ejection fraction (HFrEF), this is not the case for HF with preserved ejection fraction (HFpEF). HFpEF is a heterogeneous disease with a high variability of CVD and conventional risk factors including T2DM, hypertension, renal disease, older age, and female sex; therefore, the extrapolation of predictive abilities of traditional biomarkers on this population is constrained. New biomarker-based approaches are disputed to be sufficient for improving risk stratification and the prediction of poor clinical outcomes in patients with HFpEF. Novel biomarkers of biomechanical stress, fibrosis, inflammation, oxidative stress, and collagen turn-over have shown potential benefits in determining prognosis in T2DM patients with HF regardless of natriuretic peptides, but their role in point-to-care and in routine practice requires elucidation in large clinical trials.

scholarly journals Endothelial Dysfunction in Diabetes Mellitus: Possible Involvement of Endoplasmic Reticulum Stress?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Basma Basha ◽  
Samson Mathews Samuel ◽  
Chris R. Triggle ◽  
Hong Ding
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Clinical Trials ◽  
Endoplasmic Reticulum ◽  
Endothelial Dysfunction ◽  
Er Stress ◽  
Vascular Complications ◽  
Cardiovascular Complications ◽  
Therapeutic Agents ◽  
Recent Past

The vascular complications of diabetes mellitus impose a huge burden on the management of this disease. The higher incidence of cardiovascular complications and the unfavorable prognosis among diabetic individuals who develop such complications have been correlated to the hyperglycemia-induced oxidative stress and associated endothelial dysfunction. Although antioxidants may be considered as effective therapeutic agents to relieve oxidative stress and protect the endothelium, recent clinical trials involving these agents have shown limited therapeutic efficacy in this regard. In the recent past experimental evidence suggest that endoplasmic reticulum (ER) stress in the endothelial cells might be an important contributor to diabetes-related vascular complications. The current paper contemplates the possibility of the involvement of ER stress in endothelial dysfunction and diabetes-associated vascular complications.

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