Glucose-Lowering and Metabolic Effects of SGLT2 Inhibitors
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have consistently demonstrated improved outcomes in patients with heart failure with or without type 2 diabetes; however, the mechanisms contributing to these benefits remain poorly understood. Although SGLT2 inhibitors do have glucose-lowering effects, it is unlikely that their cardiovascular benefits are solely due to improved glycemic control. This improved glycemia leads to consequent metabolic effects that could provide further explanation for their action. This review discusses the glucose-lowering and metabolic effects of SGLT2 inhibitors and how these might lead to ...
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Authors: Ify R. Mordi, Chim C. Lang Source Type: research
Renoprotective Effects of SGLT2 Inhibitors
SGLT2 inhibitors can protect the kidneys of patients with and without type 2 diabetes from failing. This includes blood glucose dependent and independent mechanisms. SGLT2 inhibitors lower glomerular pressure and filtration, thereby reducing the physical stress on the filtration barrier and the oxygen demand for tubular reabsorption. This improves cortical oxygenation, which, together with lesser tubular glucotoxicity and improved mitochondrial function and autophagy, can reduce proinflammatory and profibrotic signaling and preserve tubular function and GFR in long term. By shifting transport downstream, SGLT2 inhibitors m...
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Authors: Volker Vallon Source Type: research
SGLT2 Inhibitors in Heart Failure with Reduced Ejection Fraction
Sodium-glucose transport inhibitors (SGLT2i) have been found to be effective in preventing heart failure in patients with diabetes or chronic kidney disease with or without cardiovascular disease. Recent evidence suggests that SGLT2i substantially improve cardiovascular and renal outcomes in patients with heart failure with reduced ejection fraction (HFrEF). In this review, we discuss the combined cardio-renal benefits of SGLT2i in patients with HFrEF. In addition, we discuss the impact of renoprotection in the midterm management of HFrEF and possible implementation strategies for initiating SGLT2i in routine care of HFrEF...
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Authors: Tripti Rastogi, Nicolas Girerd Source Type: research
Sodium-Glucose Cotransporter-2 Inhibitors: Impact on Atherosclerosis and Atherosclerotic Cardiovascular Disease Events
Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) improve the risk for heart and kidney failure. However, their effects on major atherosclerotic cardiovascular events (MACE) are less clear. Although outcomes trials of drugs for diabetes were not powered to prove superiority, the totality of trial data yields an estimate of ∼11% relative reduction for MACE (HR 0.89, 95%CI 0.82–0.96) and neutral on stroke (HR 0.92, 95%CI 0.79–1.08). In animal models, SGLT-2i favorably affects plaque size, composition, and inflammatory pathways; human data in this regard are lacking. Ongoing trials are evaluating SGLT-2i efficacy i n ...
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Authors: Adam J. Nelson, Josephine L. Harrington, Ahmed A. Kolkailah, Neha J. Pagidipati, Darren K. McGuire Source Type: research
Sodium Glucose Cotransporter 2 Inhibitors, Amputation Risk, and Fracture Risk
Sodium glucose cotransporter 2 (SGLT2) inhibitors are associated with cardiovascular and renal benefits across a broad range of patients, with no increase in total serious adverse events. We evaluated the evidence with respect to amputation and fracture risks for this drug class. Overall, SGLT2 inhibitors are not associated with an increased risk of amputation or fracture in any of the patient populations they have been tested in. The increase in amputation and fracture risks with canagliflozin observed in the CANagliflozin cardioVascular Assessment Study (CANVAS) program was not seen in the Canagliflozin and Renal Events ...
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Authors: Clare Arnott, Robert A. Fletcher, Bruce Neal Source Type: research
SGLT2 Inhibitors in Type 2 Diabetes Mellitus
Sodium-glucose cotransporter 2 inhibitors were first discovered as glucose-lowering drugs because of their glycosuric action and good safety profile. Subsequently, they were studied in cardiovascular outcome trials in people with type 2 diabetes, and their cardiovascular benefit was consistently observed as regards heart failure hospitalizations and cardiovascular death. Investigation of the underlying mechanisms granting such benefit is continuously engaging researchers all over the world. The findings described in this article paved the way to a larger use of these drugs in patients with heart failure, with the aim of im...
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Authors: Giulia Ferrannini, Gianluigi Savarese, Francesco Cosentino Source Type: research
SGLT2 Inhibitors and Heart Failure with Preserved Ejection Fraction
The trials of SLGT2 inhibitors in type 2 diabetes suggested a potential benefit of these drugs in patients with heart failure. When randomized trials confirmed their benefit in heart failure with reduced ejection fraction, attention turned to heart failure with preserved ejection fraction (HFPEF). In the EMPEROR-Preserved trial the SGLT2 inhibitor empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure (HR 0.79 95%CI 0.69 –0.9, P (Source: Heart Failure Clinics)
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Authors: Pardeep S. Jhund Source Type: research
Sodium-glucose Cotransporter 2 Inhibitors and Nonalcoholic Fatty Liver Disease
Nonalcoholic fatty liver disease (NAFLD) is a systemic disorder with cardiovascular manifestations; due to its complex and multifactorial pathophysiological mechanisms, no effective pharmacologic treatment has been identified to date. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated potentially favorable effects on NAFLD incidence and progression in preclinical and clinical studies. This review summarizes the evidence from preclinical and human studies supporting the use of SGLT2 inhibitors in NAFLD and proposes several mechanisms that may drive these favorable effects (ie, increasing insulin sensitivity...
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Authors: Husam M. Salah, Marat Fudim Source Type: research
SGLT2 Inhibitors Are Lifesavers in Heart Failure
The first three trials of sodium-glucose cotransporter-2 (SGLT2) inhibitors investigating cardiovascular (CV) safety, as required by the Food and Drug Administration, all revealed an unexpected approximate 30% reduction in heart failure (HF) hospitalizations in patients with type 2 diabetes mellitus (T2DM) with and at risk for CV disease.1 –3 However, these drugs were not associated with decreased stroke risk or reductions in myocardial infarction. These findings piqued the interest of HF specialists and led to clinical trials specifically investigating the effects of SGLT2 inhibitors in patients with HF (Fig. 1). (Sour...
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Authors: Ragavendra R. Baliga, Deepak L. Bhatt, Eduardo Bossone Tags: Preface Source Type: research
SGLT-2 Inhibitors
HEART FAILURE CLINICS (Source: Heart Failure Clinics)
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Authors: Ragavendra R. Baliga, Deepak L. Bhatt Source Type: research
Copyright
ELSEVIER (Source: Heart Failure Clinics)
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Source Type: research
Contributors
EDUARDO BOSSONE, MD, PhD, FCCP, FESC, FACCConsulting Editor, Heart Failure Clinics, Director, Division of Cardiology, AORN Antonio Cardarelli Hospital, Naples, Italy (Source: Heart Failure Clinics)
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Source Type: research
Contents
Ragavendra R. Baliga, Deepak L. Bhatt, and Eduardo Bossone (Source: Heart Failure Clinics)
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Source Type: research
Forthcoming Issues
Challenges in Pulmonary Hypertension (Source: Heart Failure Clinics)
Source: Heart Failure Clinics - October 1, 2022 Category: Cardiology Source Type: research
SGLT2 Inhibitors and Peripheral Vascular Events
Fifty articles comprising 18 randomized controlled trials (RCTs), 16 observational studies, and 16 meta-analyses on the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors were evaluated in the current review. Only one-fourth of the cohorts of recent trials had peripheral arterial disease (PAD), whereas this subgroup was at high risk for amputations. Despite a remarkable heterogeneity of RCTs, only 2 trials on canagliflozin suggested excess amputation rates, whereas several observational studies generated conflicting conclusions and remained short on possible explanations. Preliminary evidence from observ...
Source: Heart Failure Clinics - August 12, 2022 Category: Cardiology Authors: Elena Marchiori, Roman N. Rodionov, Frederik Peters, Christina Magnussen, Joakim Nordanstig, Alexander Gombert, Konstantinos Spanos, Natalia Jarzebska, Christian-Alexander Behrendt Source Type: research
