scholarly journals Perspective of the β-blockers for the patients with diabetes and heart failure 

2020 ◽  
Vol 8 (4) ◽  
pp. 97-99
Author(s):  
Hiroshi BANDO
Keyword(s):  
Heart Failure ◽  
Adverse Outcomes ◽  
Control Group ◽  
Sodium Glucose Cotransporter ◽  
Strict Glycemic Control ◽  
Cardiovascular Assessment ◽  
Patients With Diabetes ◽  
Outcome Trial ◽  
Β Blockers

Patients with diabetes and heart failure have been increasing due to Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD) study. β-blockers showed significantly suppressed cardiovascular events in the strict glycemic control group. Sodium-glucose Cotransporter-2 Inhibitors (SGLT2i) seem to be beneficial for diabetes and heart failure. Clinical efficacy of β-blockers would be suggested from three studies including Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients-Removing Excess Glucose (EMPA-REG OUTCOME) trial, Canagliflozin cardioVascular Assessment Study (CANVAS) and Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) study. Further discussion will be expected with research in detail.

scholarly journals Treatment of Heart Failure with Sodium-Glucose Cotransporter 2 Inhibitors and Other Anti-diabetic Drugs

2019 ◽  
Vol 5 (1) ◽  
pp. 27-30 ◽  
Author(s):  
Thomas A Zelniker ◽  
Eugene Braunwald
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Renal Failure ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk ◽  
Patients With Diabetes ◽  
Glucagon Like Peptide 1

Patients with type 2 diabetes are at increased risk of developing heart failure, cardiovascular death and renal failure. The recent results of three large sodium-glucose cotransporter 2 inhibitor cardiovascular outcomes trials have demonstrated a reduction in heart failure hospitalisation and progressive renal failure. One trial also showed a fall in cardiovascular and total death. A broad spectrum of patients with diabetes benefit from these salutary effects in cardiac and renal function and so these trials have important implications for the management of patients with type 2 diabetes. Selected glucagon-like peptide 1 receptor agonists have also been shown to reduce adverse cardiovascular outcomes.

scholarly journals Sodium–glucose Cotransporter 2 Inhibitors in Heart Failure: Potential Mechanisms of Action, Adverse Effects and Future Developments

2019 ◽  
Vol 14 (1) ◽  
pp. 23-32 ◽  
Author(s):  
Juan Tamargo
Keyword(s):  
Heart Failure ◽  
Glycaemic Control ◽  
Adverse Effects ◽  
Major Cardiovascular Events ◽  
Sodium Glucose Cotransporter ◽  
Urinary Glucose ◽  
Patients With Diabetes ◽  
Near Future ◽  
Glucose Excretion

Heart failure is a common complication in patients with diabetes, and people with both conditions present a worse prognosis. Sodium– glucose cotransporter 2 inhibitors (SGLT2Is) increase urinary glucose excretion, improving glycaemic control. In type 2 diabetes (T2D), some SGLT2Is reduce major cardiovascular events, heart failure hospitalisations and worsening of kidney function independent of glycaemic control. Multiple mechanisms (haemodynamic, metabolic, hormonal and direct cardiac/renal effects) have been proposed to explain these cardiorenal benefits. SGLT2Is are generally well tolerated, but can produce rare serious adverse effects, and the benefit/risk ratio differs between SGLT2Is. This article analyses the mechanisms underlying the cardiorenal benefits and adverse effects of SGLT2Is in patients with T2D and heart failure and outlines some questions to be answered in the near future.

scholarly journals Lessons learned from the DAPA-HF trial concerning the mechanisms of benefit of SGLT2 inhibitors on heart failure events in the context of other large-scale trials nearing completion

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Milton Packer
Keyword(s):  
Heart Failure ◽  
Large Scale ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Adverse Outcomes ◽  
Lessons Learned ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Artery Disease

Abstract Four large-scale trials in type 2 diabetes have shown that sodium-glucose cotransporter 2 (SGLT2) inhibitors prevent the occurrence of serious heart failure events. Additionally, the DAPA-HF trial demonstrated a benefit of dapagliflozin to reduce major adverse outcomes in patients with established heart failure with a reduced ejection fraction. The trial sheds light on potential mechanisms. In DAPA-HF, the benefits of dapagliflozin on heart failure were seen to a similar extent in both patients with or without diabetes, thus undermining the hypothesis that these drugs mitigate glycemia-related cardiotoxicity. 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. Also, dapagliflozin does not have a meaningful effect to decrease circulating natriuretic peptides, and it did not potentiate the actions of diuretics in DAPA-HF; moreover, intensification of diuretics therapy does not reduce cardiovascular death, questioning a benefit of SGLT2 inhibitors that is mediated by an action on renal sodium excretion. Finally, although hematocrit increases with SGLT2 inhibitors might favorably affect patients with coronary artery disease, in DAPA-HF, the benefit of dapagliflozin was similar in patients with or without an ischemic cardiomyopathy; furthermore, increases in hematocrit do not favorably affect the clinical course of patients with heart failure. Therefore, the results of DAPA-HF do not support many currently-held hypotheses about the mechanism of action of SGLT2 inhibitors in heart failure. Ongoing trials are likely to provide further insights.

scholarly journals Benefit of Canagliflozin In Patients With Type 2 Diabetes After Hospitalization For Acute Heart Failure

2020 ◽  
Author(s):  
Ernesto Martin Dorado ◽  
José López-Aguilera ◽  
Rafael González ◽  
Manuel Anguita ◽  
Guillermo Gutiérrez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Acute Heart Failure ◽  
Sglt2 Inhibitors ◽  
Control Group ◽  
First Year ◽  
Cardiovascular Morbidity And Mortality ◽  
Patients With Diabetes

Abstract BACKGROUND: Heart failure (HF) is one of the mayor contributors to cardiovascular morbidity and mortality in patients with diabetes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated to reduce the risk of hospitalization for HF in patients with type 2 diabetes mellitus. We aimed to compare the incidence of readmission in patients who received canagliflozin at discharge after hospitalization of acute HF and changes in N-terminal pro–B-type natriuretic peptide (NT-ProBNP) concentration during follow-up. METHODS: We retrospectively included 102 consecutive patients with diabetes discharged for acute heart failure and without contraindications for SGLT2 inhibitors. We divided them in two groups: 45 patients with canagliflozin at discharge therapy and 57 without any SGLT2 inhibitors.RESULTS: Over a median follow-up of 22 months, 45 (44.1%) were hospitalized for HF. Most of the patients who were readmitted due to heart failure occurred during the first year (37.3%). HF readmission at first year occurred in 10 patients (22.2%) in canagliflozin group and 29 patients (49.1%) in control group (HR: 0.45; 95% CI: 0.21–0.96; p < 0.039) after multivariate adjustment. A composite outcome of hospitalization for HF or death for cardiovascular causes was lower in canagliflozin group (37.8%) than in the control group (70.2%) (HR: 0.51; 95% CI: 0.27–0.95; p < 0.035). Analysis of NT-ProBNP concentration showed an interaction between canagliflozin therapy and follow-up time (p=0.002).CONCLUSIONS: Canagliflozin therapy at discharge was associated with lower risk of readmission for HF and a reduction of NT-ProBNP concentration in patients with diabetes after hospitalization for HF.

scholarly journals Impact of Canagliflozin in Patients with Type 2 Diabetes after Hospitalization for Acute Heart Failure: A Cohort Study

2021 ◽  
Vol 10 (3) ◽  
pp. 505
Author(s):  
Ernesto Martín ◽  
José López-Aguilera ◽  
Rafael González-Manzanares ◽  
Manuel Anguita ◽  
Guillermo Gutiérrez ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Death ◽  
Sglt2 Inhibitors ◽  
Control Group ◽  
First Year ◽  
Cardiovascular Morbidity And Mortality ◽  
Patients With Diabetes

Background: Heart failure (HF) is one of the mayor contributors to cardiovascular morbidity and mortality in patients with diabetes. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated to reduce the risk of hospitalization for HF in patients with type 2 diabetes mellitus (T2D). We aimed to assess the risk for re-hospitalization in a cohort of patients hospitalized for HF according to whether or not they received canagliflozin at discharge, as well as changes in N-terminal pro–B-type natriuretic peptide (NT-ProBNP) concentration during follow-up. Methods: We conducted a retrospective longitudinal study at a tertiary centre including 102 consecutive T2D patients discharged for acute HF without contraindication for SGLT2 inhibitors. We compared adverse clinical events (HF rehospitalization and cardiovascular death) and NT-ProBNP changes according to canagliflozin prescription at discharge. Results: Among the 102 patients included, 45 patients (44.1%) were prescribed canagliflozin and the remaining 57 (55.9%) were not prescribed any SGLT2 inhibitors (control group). After a median follow-up of 22 months, 45 patients (44.1%) were hospitalized for HF. Most of the rehospitalizations occurred during the first year (37.3%). HF readmission at first year occurred in 10 patients (22.2%) in the canagliflozin group and 29 patients (49.1%) in the control group (hazard ratio (HR): 0.45; 95% confidence interval (CI): 0.21–0.96; p < 0.039). A composite outcome of hospitalization for HF or death from cardiovascular causes was lower in the canagliflozin group (37.8%) than in the control group (70.2%) (HR: 0.51; 95% CI: 0.27–0.95; p < 0.035). Analysis of NT-ProBNP concentration showed an interaction between canagliflozin therapy and follow-up time (p = 0.002). Conclusions: Canagliflozin therapy at discharge was associated with a lower risk of readmission for HF and a reduction in NT-ProBNP concentration in patients with diabetes after hospitalization for HF.

scholarly journals Effect of Luseogliflozin on Heart Failure With Preserved Ejection Fraction in Patients With Diabetes Mellitus

2020 ◽  
Vol 9 (16) ◽  
Author(s):  
Kentaro Ejiri ◽  
Toru Miyoshi ◽  
Hajime Kihara ◽  
Yoshiki Hata ◽  
Toshihiko Nagano ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Significant Difference ◽  
Patients With Diabetes ◽  
To Receive

Background Effects of sodium‐glucose cotransporter 2 inhibitors on reducing hospitalization for heart failure have been reported in randomized controlled trials, but their effects on patients with heart failure with preserved ejection fraction ( HF p EF ) are unknown. This study aimed to evaluate the drug efficacy of luseogliflozin, a sodium‐glucose cotransporter 2 inhibitor, in patients with type 2 diabetes mellitus and HF p EF . Methods and Results We performed a multicenter, open‐label, randomized, controlled trial for comparing luseogliflozin 2.5 mg once daily with voglibose 0.2 mg 3 times daily in patients with type 2 diabetes mellitus suffering from HF p EF (left ventricular ejection fraction >45% and BNP [B‐type natriuretic peptide] concentrations ≥35 pg/mL) in a 1:1 randomization fashion. The primary outcome was the difference from baseline in BNP levels after 12 weeks of treatment between the 2 drugs. A total of 173 patients with diabetes mellitus and HF p EF were included. Of these, 83 patients were assigned to receive luseogliflozin and 82 to receive voglibose. There was no significant difference in the reduction in BNP concentrations after 12 weeks from baseline between the 2 groups. The ratio of the mean BNP value at week 12 to the baseline value was 0.79 in the luseogliflozin group and 0.87 in the voglibose group (percent change, −9.0% versus −1.9%; ratio of change with luseogliflozin versus voglibose, 0.93; 95% CI, 0.78–1.10; P =0.26). Conclusion In patients with type 2 diabetes mellitus and HF p EF , there is no significant difference in the degree of reduction in BNP concentrations after 12 weeks between luseogliflozin and voglibose. Registration URL : https://www.umin.ac.jp/ctr/index.htm ; Unique identifier: UMIN 000018395.

scholarly journals Cardiometabolic Risk Reduction: A Review of Clinical Guidelines and the Role of SGLT-2 Inhibitors

2021 ◽  
Vol 70 (6 Supplement) ◽  
Author(s):  
Reid
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Cardiometabolic Risk ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes ◽  
Recommended Therapy

At the end of the activity, participants will be able to: • Identify how heart failure (HF), chronic kidney disease (CKD), and type 2 diabetes mellitus (T2DM) and associated cardiovascular (CV) risks are interconnected. • Initiate guideline-recommended therapy to reduce CV risk in patients with HF, CKD, and/or T2DM. • Apply evidence for sodium-glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) to clinical practice, based on recent and emerging trials. • Review evidence suggesting increased incidence and severity of COVID-19 infection in patients with diabetes.

scholarly journals Sodium-glucose cotransporter type 2 inhibitors: successful running after two hares

2021 ◽  
Vol 26 (2S) ◽  
pp. 4534
Author(s):  
N. B. Perepech ◽  
I. E. Mikhailova
Keyword(s):  
Heart Failure ◽  
Cardiovascular Events ◽  
Large Scale ◽  
Randomized Clinical Trials ◽  
Drug Action ◽  
Sglt2 Inhibitors ◽  
Reduced Ejection Fraction ◽  
Sodium Glucose Cotransporter ◽  
Patients With Diabetes

The review is devoted to the clinical efficacy of sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Information on the mechanisms of drug action is given, as well as rationale for their use in the management of patients with diabetes and heart failure (HF) is provided. The results of large-scale randomized clinical trials evaluating the efficacy of SGLT2 inhibitors are discussed. We showed the beneficial effect of SGLT-2 inhibitors on the risk of cardiovascular events in patients with type 2 diabetes. In addition, an evidence of the ability of dapagliflozin and empagliflozin to improve the prognosis of patients with HF with reduced ejection fraction without diabetes are presented. The evidence and mechanisms of the nephroprotective action of SGLT2 inhibitors in patients with diabetes and HF are considered.

scholarly journals Cardiac effects of SGLT2 inhibitors: the sodium hypothesis

2017 ◽  
Vol 114 (1) ◽  
pp. 12-18 ◽  
Author(s):  
Edoardo Bertero ◽  
Leticia Prates Roma ◽  
Pietro Ameri ◽  
Christoph Maack
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ketone Bodies ◽  
Supply And Demand ◽  
Current Evidence ◽  
Diabetes Research ◽  
Metabolic Switch ◽  
Sodium Glucose Cotransporter ◽  
Outcome Trial

Abstract The effects of intense glycaemic control on macrovascular complications in patients with type 2 diabetes are incompletely resolved, and many glucose-lowering medications negatively affect cardiovascular outcomes. Recently, the EMPA-REG OUTCOME trial revealed that empagliflozin, an inhibitor of the sodium-glucose cotransporter 2 (SGLT2), substantially reduced the risk of hospitalization for heart failure, death from cardiovascular causes, and all-cause mortality in patients with type 2 diabetes mellitus at high cardiovascular risk. Although several mechanisms may explain this benefit, plasma volume contraction and a metabolic switch favouring cardiac ketone bodies oxidation have recently been proposed as the major drivers. Recent experimental work has prompted a novel and intriguing hypothesis, according to which empagliflozin may reduce intracellular sodium (Na+) load observed in failing cardiac myocytes by inhibiting the sarcolemmal Na+/H+ exchanger. Since elevated intracellular Na+ hampers mitochondrial Ca2+ handling and thereby, deteriorates energy supply and demand matching and the mitochondrial antioxidative defence systems, empagliflozin may positively affect cardiac function by restoring mitochondrial function, and redox state in the failing heart. Here, we review the current evidence for such a third mechanistic hypothesis, which may foster heart failure and diabetes research into a new direction which harbours several potential targets for therapeutic intervention.

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.

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