scholarly journals Treatment of Patients with Heart failure and Type 2 Diabetes: a review of the literature

2019 ◽  
Vol 13 (4) ◽  
pp. 205-224
Author(s):  
Elisa Fabbri ◽  
Maurizio Nizzoli
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Sglt2 Inhibitors ◽  
New Drugs ◽  
Review Of The Literature ◽  
Glucose Lowering ◽  
Promising Tool ◽  
Patients With Heart Failure ◽  
Underlying Mechanisms

Heart failure (HF) and type 2 diabetes (T2D) often coexist and having both the diseases compared to having one alone is associated with greater challenges in their management/treatment and worse outcomes. The present review of the literature is aimed at providing a comprehensive synopsis of the main evidences about the treatment of the two coexisting conditions. In particular, the recent introduction of new glucose-lowering drugs has been deeply changing the therapeutic approach to T2D. Big randomized controlled trails (RCTs) developed to test the cardiovascular safety of these new drugs consistently highlighted a reduction of the risk of hospitalization for HF in patients with T2D treated with sodium-glucose co-transporter 2 (SGLT2) inhibitors, suggesting a potential and revolutionary class effect probably related to their diuretic effect. Moreover, a renal protective effect of this drug class has also been emerging and the beneficial effect of SGLT2 inhibitors on the risk of HF hospitalization seems to be even greater in patients with worse renal function. In conclusion, although the underlying mechanisms are not fully understood, SGLT2 inhibitors appear to be a promising tool to treat HF and T2D. Ongoing RCTs specifically enrolling patients with HF treated with SGLT2 inhibitors will provide more insights and further information.

scholarly journals Effect of canagliflozin on N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes and chronic heart failure according to baseline use of glucose-lowering agents

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Atsushi Tanaka ◽  
Shigeru Toyoda ◽  
Takumi Imai ◽  
Kazuki Shiina ◽  
Hirofumi Tomiyama ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Left Ventricular ◽  
Sglt2 Inhibitors ◽  
Left Ventricular Ejection ◽  
Glucose Lowering

Abstract Background Sodium–glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of a deterioration in heart failure (HF) and mortality in patients with a broad range of cardiovascular risks. Recent guidelines recommend considering the use of SGLT2 inhibitors in patients with type 2 diabetes (T2D) and HF, irrespective of their glycemic control status and background use of other glucose-lowering agents including metformin. However, only a small number of studies have investigated whether the effects of SGLT2 inhibitor in these patients differ by the concomitant use of other glucose-lowering agents. Methods This was a post-hoc analysis of the CANDLE trial (UMIN000017669), an investigator-initiated, multicenter, open-label, randomized, controlled trial. The primary aim of the analysis was to assess the effect of 24 weeks of treatment with canagliflozin, relative to glimepiride, on N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration in patients with T2D and clinically stable chronic HF. In the present analysis, the effect of canagliflozin on NT-proBNP concentration was assessed in the patients according to their baseline use of other glucose-lowering agents. Results Almost all patients in the CANDLE trial presented as clinically stable (New York Heart Association class I to II), with about 70% of participants having HF with a preserved ejection fraction phenotype (defined as a left ventricular ejection fraction ≥ 50%) at baseline. Of the 233 patients randomized to either canagliflozin (100 mg daily) or glimepiride (starting dose 0.5 mg daily), 85 (36.5%) had not been taking any glucose-lowering agents at baseline (naïve). Of the 148 patients who had been taking at least one glucose-lowering agent at baseline (non-naïve), 44 (29.7%) and 127 (85.8%) had received metformin or a dipeptidyl dipeptidase-4 (DPP-4) inhibitor, respectively. The group ratio (canagliflozin vs. glimepiride) of proportional changes in the geometric means of NT-proBNP concentration was 0.95 (95% confidence interval [CI] 0.76 to 1.18, p = 0.618) for the naïve subgroup, 0.92 (95% CI 0.79 to1.07, p = 0.288) for the non-naïve subgroup, 0.90 (95% CI 0.68 to 1.20, p = 0.473) for the metformin-user subgroup, and 0.91 (95% CI 0.77 to 1.08, p = 0.271) for the DPP-4 inhibitor-user subgroup. No heterogeneity in the effect of canagliflozin, relative to glimepiride, on NT-proBNP concentration was observed in the non-naïve subgroups compared to that in the naïve subgroup. Conclusion The impact of canagliflozin treatment on NT-proBNP concentration appears to be independent of the background use of diabetes therapy in the patient population examined. Trial registration University Medical Information Network Clinical Trial Registry, number 000017669. Registered on May 25, 2015

scholarly journals Sodium-glucose cotransporter 2 inhibitor effects on cardiovascular outcomes in chronic kidney disease

2020 ◽  
Vol 35 (Supplement_1) ◽  
pp. i43-i47 ◽  
Author(s):  
Oshini Shivakumar ◽  
Naveed Sattar ◽  
David C Wheeler
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Major Adverse Cardiovascular Event ◽  
Sglt2 Inhibitors ◽  
Adverse Cardiovascular Event ◽  
Sodium Glucose Cotransporter ◽  
Patients With Heart Failure

Abstract Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce cardiovascular events, specifically those related to heart failure in patients with type 2 diabetes. Reductions in major adverse cardiovascular event (MACE) outcomes are also observed, but confined largely to patients who have prior cardiovascular disease. Cardiovascular outcome benefits extend to patients with type 2 diabetes and reduced estimated glomerular filtration (eGFR) rate down to 30 mL/min/1.73 m2 and to patients with heart failure but without diabetes. Ongoing trials are exploring whether patients with chronic kidney disease (CKD) but without diabetes will gain similar benefits from this class of agents. Although some safety concerns have emerged, it seems likely that SGLT2 inhibitors will be used more widely in CKD patients to reduce their cardiovascular risk.

scholarly journals PRIORITIES OF ANTI-HYPERGLYCAEMIC DRUG THERAPY IN PATIENTS WITH TYPE 2 DIABETES AND HEART FAILURE

2020 ◽  
Vol 73 (3) ◽  
pp. 609-613
Author(s):  
Мaryana М. Rоsul ◽  
Мiroslava М. Bletskan ◽  
Nataliya V. Ivano ◽  
Marina O. Korabelschykova ◽  
Yelyzaveta І. Rubtsova
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Large Scale ◽  
Cardiovascular Complications ◽  
Glucose Lowering ◽  
Wall Stiffness ◽  
Patients With Heart Failure ◽  
Patients With Diabetes

The aim is to explore the possibilities of improving the effectiveness in preventing cardiovascular diseases and heart failure using sodium-glucose co-transporter 2 inhibitors. Materials and methods: The analysis of the existing clinical and experimental data on the effect of sodium-glucose co-transporter 2 (SGLT-2) inhibitors on the cardiovascular system, the condition of kidneys, cardiovascular risk factors. Review: SGLT-2 inhibitors are the first class of glucose-lowering agents in large-scale studies (EMPA-REG OUTCOME, CANVAS, CVD-REAL, CVD-REAL2) which have demonstrated the ability to improve cardiorenal outcomes and reduce the risk of hospitalization with heart failure in patients with diabetes. In addition to hypoglycaemic action, SGLT-2 inhibitors show a number of pleiotropic effects, which are potentially capable of reducing cardiovascular risk: diuretic effect, decrease in: blood pressure, arterial wall stiffness, waist and body weight, expression of albuminuria, etc. The use of drugs of this class opens great prospects not only in terms of glycaemic control, but also in the prevention of cardiovascular complications of diabetes. Conclusions: 1. When choosing glucose-lowering agents in patients with type 2 diabetes, it is necessary to take into account their impact on the risk of development and the course of heart failure. 2. SGLT-2 inhibitors ought to be considered as a preferred method of treatment for type 2 diabetes in patients with heart failure or with a risk of heart failure that meets the latest recommendations of the European and American Diabetes Association.

scholarly journals SGLT2 Inhibitors and Their Mode of Action in Heart Failure—Has the Mystery Been Unravelled?

2021 ◽  
Author(s):  
Steffen Pabel ◽  
Nazha Hamdani ◽  
Mark Luedde ◽  
Samuel Sossalla
Keyword(s):  
Heart Failure ◽  
Clinical Evidence ◽  
Ion Homeostasis ◽  
Cardiac Contractility ◽  
Sglt2 Inhibitors ◽  
New Drugs ◽  
Metabolic Effects ◽  
Patients With Heart Failure ◽  
Underlying Mechanisms ◽  
And Oxidative Stress

Abstract Purpose of review SGLT2 inhibitors (SGLT2i) are new drugs for patients with heart failure (HF) irrespective of diabetes. However, the mechanisms of SGLT2i in HF remain elusive. This article discusses the current clinical evidence for using SGLT2i in different types of heart failure and provides an overview about the possible underlying mechanisms. Recent findings Clinical and basic data strongly support and extend the use of SGLT2i in HF. Improvement of conventional secondary risk factors is unlikely to explain the prognostic benefits of these drugs in HF. However, different multidirectional mechanisms of SGLT2i could improve HF status including volume regulation, cardiorenal mechanisms, metabolic effects, improved cardiac remodelling, direct effects on cardiac contractility and ion-homeostasis, reduction of inflammation and oxidative stress as well as an impact on autophagy and adipokines. Summary Further translational studies are needed to determine the mechanisms of SGLT2i in HF. However, basic and clinical evidence encourage the use of SGLT2i in HFrEF and possibly HFpEF.

scholarly journals Glucose Lowering Strategies for Cardiac Benefits: Pathophysiological Mechanisms

Physiology ◽  
2018 ◽  
Vol 33 (3) ◽  
pp. 197-210 ◽  
Author(s):  
Harpreet S. Bajaj ◽  
Bernard Zinman
Keyword(s):  
Type 2 Diabetes ◽  
Current Knowledge ◽  
Sglt2 Inhibitors ◽  
Future Research ◽  
Knowledge Gaps ◽  
Glucose Lowering ◽  
Pathophysiological Mechanisms ◽  
Underlying Mechanisms ◽  
Review Current

Recent trials in Type 2 diabetes (T2D) have shown cardiovascular benefits with specific GLP-1 receptor agonists and SGLT2 inhibitors. We discuss the landscape of outcome trials in T2D from a pathophysiology viewpoint, review current knowledge gaps in underlying mechanisms, propose a caloric fuel routing hypothesis, and highlight areas of future research.

scholarly journals Dapagliflozin – structure, synthesis, and new indications

Pharmacia ◽  
2021 ◽  
Vol 68 (3) ◽  
pp. 591-596
Author(s):  
Stefan Balkanski
Keyword(s):  
Heart Failure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Sglt2 Inhibitors ◽  
Glucose Lowering ◽  
Structure Activity ◽  
Structure Synthesis ◽  
Patients With Heart Failure ◽  
Positive Effect

Dapagliflozin is a sodium-glucose co-transporter-2 (SGLT2) inhibitors used in the treatment of patients with type 2 diabetes. An aryl glycoside with significant effect as glucose-lowering agents, Dapagliflozin also has indication for patients with Heart Failure and Chronic Kidney Disease. This review examines the structure, synthesis, analysis, structure activity relationship and uses of the product. The studies behind this drug have opened the doors for the new line of treatment – a drug that reduces blood glucoses, decreases the rate of heart failures, and has a positive effect on patients with chronic kidney disease.

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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