Emerging horizons: clinical applications and multifaceted benefits of SGLT-2 inhibitors beyond diabetes DOI Creative Commons
Qing Feng,

Moya Wu,

Zizhao Mai

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: March 20, 2025

SGLT-2 inhibitors, initially developed for type 2 diabetes, demonstrate profound cardiorenal and metabolic benefits. This review synthesizes evidence from clinical trials mechanistic studies to elucidate their roles in cardiovascular diseases, chronic kidney disease, non-alcoholic fatty liver disease. Key findings include a notable reduction death/heart failure hospitalization, marked decrease heart hospitalization risk, significant improvements renal hepatic outcomes. Emerging mechanisms, such as autophagy induction, ketone utilization, anti-inflammatory effects, underpin these Ongoing explore potential non-diabetic populations, positioning inhibitors transformative agents multisystem disease management.

Language: Английский

Outcomes in diabetic patients treated with SGLT2-Inhibitors with acute myocardial infarction undergoing PCI: The SGLT2-I AMI PROTECT Registry DOI Creative Commons
Pasquale Paolisso, Luca Bergamaschi, Felice Gragnano

et al.

Pharmacological Research, Journal Year: 2022, Volume and Issue: 187, P. 106597 - 106597

Published: Dec. 5, 2022

To investigate in-hospital and long-term prognosis in T2DM patients presenting with acute myocardial infarction (AMI) treated SGLT2-I versus other oral anti-diabetic agents (non-SGLT2-I users).

Language: Английский

Citations

88
Anti-inflammatory role of SGLT2 inhibitors as part of their anti-atherosclerotic activity: Data from basic science and clinical trials DOI Creative Commons
Lucia Scisciola,

Vittoria Cataldo,

Fatemeh Taktaz

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Sept. 6, 2022

Atherosclerosis is a progressive inflammatory disease leading to mortality and morbidity in the civilized world. manifests as an accumulation of plaques intimal layer arterial wall that, by its subsequent erosion or rupture, triggers cardiovascular diseases. Diabetes mellitus well-known risk factor for atherosclerosis. Indeed, Type 2 diabetes patients have increased atherosclerosis associated-cardiovascular complications than non-diabetic patients. Sodium-glucose co-transport inhibitors (SGLT2i), novel anti-diabetic drugs, surprising advantage effects, such reducing death patient with without diabetes. Numerous studies shown that due significant burden SGLT2i may play role inflammation. In fact, several experiment results demonstrated SGLT2i, suppression mechanism, slows progression Therefore, double benefit terms glycemic control atherosclerotic process at myocardial vascular level. This review elaborates on anti-inflammatory effects sodium-glucose co-transporter

Language: Английский

Citations

80
Sodium Glucose Cotransporter-2 Inhibitor Empagliflozin Reduces Infarct Size Independently of Sodium Glucose Cotransporter-2 DOI
Sha Chen, Qian Wang,

Andriana Christodoulou

et al.

Circulation, Journal Year: 2023, Volume and Issue: 147(3), P. 276 - 279

Published: Jan. 17, 2023

Language: Английский

Citations

61
Cardioprotective Effect of Empagliflozin and Circulating Ketone Bodies During Acute Myocardial Infarction DOI
Carlos G. Santos‐Gallego, Juan Antonio Requena-Ibáñez, Belén Picatoste

et al.

Circulation Cardiovascular Imaging, Journal Year: 2023, Volume and Issue: 16(4)

Published: April 1, 2023

SGLT2i (sodium-glucose cotransporter-2 inhibitors) improve clinical outcomes in patients with heart failure, but the mechanisms of action are not completely understood. increases circulating levels ketone bodies, which has been demonstrated to enhance myocardial energetics and induce reverse ventricular remodeling. However, role or bodies on ischemia reperfusion injury remains dark. The objective this study is investigate cardioprotective potential empagliflozin during acute infarction (MI).We used a nondiabetic porcine model using percutaneous occlusion proximal left anterior descending artery for 45 minutes. Animals received 1-week pretreatment either placebo prior MI induction. Additionally, third group intravenous infusion body BOHB (beta-hydroxybutyrate) Acute effects treatments were assessed 4-hour post-MI by cardiac magnetic resonance histology (thioflavin area at risk, triphenyltetrazolium chloride staining size). All animals euthanized immediately postcardiac resonance, samples collected.The risk was similar all groups. Empagliflozin treatment increased levels. Empagliflozin-treated showed significantly higher salvage, smaller size (both histology), less microvascular obstruction, improved function (left ventricle ejection fraction strain). Furthermore, empagliflozin-treated reduced biomarkers cardiomyocyte apoptosis oxidative stress compared placebo. results group.One-week ameliorates injury, reduces preserves systolic function, lowers stress. Periprocedural also induces cardioprotection, suggesting availability as an additional mechanism within wide spectrum actions SGLT2i.

Language: Английский

Citations

57
Contemporary pharmacological treatment and management of heart failure DOI
Biykem Bozkurt

Nature Reviews Cardiology, Journal Year: 2024, Volume and Issue: 21(8), P. 545 - 555

Published: March 26, 2024

Language: Английский

Citations

25
Left Ventricular Function, Congestion, and Effect of Empagliflozin on Heart Failure Risk After Myocardial Infarction DOI Creative Commons
Jacob A. Udell, Mark C. Petrie, W. Schuyler Jones

et al.

Journal of the American College of Cardiology, Journal Year: 2024, Volume and Issue: 83(23), P. 2233 - 2246

Published: April 6, 2024

Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days acute myocardial infarction (AMI). To evaluate association between left ventricular ejection fraction (LVEF), congestion, or both on outcomes and impact empagliflozin in reducing HF post-MI. In EMPACT-MI trial, patients were randomized an AMI complicated by either newly reduced LVEF<45%, to 10 mg daily placebo followed for a median 17.9 months. Among 6522 patients, mean baseline LVEF was 41%+9%; 2648 (40.6%) presented with LVEF<45% alone, 1483 (22.7%) congestion 2181 (33.4%) both. arm, multivariable adjusted each 10-point reduction included death hospitalization (hazard ratio [HR] 1.49; 95%CI, 1.31-1.69; P<0.0001), first (HR, 1.64; 1.37-1.96; total (rate [RR], 1.89; 1.51-2.36; P<0.0001). Presence also associated significantly higher these (HR 1.52, 1.94, RR 2.03, respectively). 0.77, 95%CI 0.60-0.98) (RR 0.67, 0.50-0.89) hospitalization, irrespective The safety profile consistent across status. AMI, severity LV dysfunction presence worse outcomes. range without congestion.

Language: Английский

Citations

18
Left Ventricular Remodeling after Myocardial Infarction: From Physiopathology to Treatment DOI Creative Commons
Sabina Andreea Leancă,

Daniela Crișu,

Antoniu Octavian Petriș

et al.

Life, Journal Year: 2022, Volume and Issue: 12(8), P. 1111 - 1111

Published: July 24, 2022

Myocardial infarction (MI) is the leading cause of death and morbidity worldwide, with an incidence relatively high in developed countries rapidly growing developing countries. The most common MI rupture atherosclerotic plaque subsequent thrombotic occlusion coronary circulation. This causes cardiomyocyte myocardial necrosis, inflammation fibrosis. Current therapies aim to restore flow by thrombus dissolution pharmaceutical treatment and/or intravascular stent implantation counteract neurohormonal activation. Despite these therapies, injury caused ischemia leads left ventricular remodeling; this process involves changes cardiac geometry, dimension function eventually progression heart failure (HF). review describes pathophysiological mechanism that remodeling therapeutic strategies a role slowing improving structure function.

Language: Английский

Citations

69
In-hospital arrhythmic burden reduction in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: Insights from the SGLT2-I AMI PROTECT study DOI Creative Commons
Arturo Cesaro, Felice Gragnano, Pasquale Paolisso

et al.

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: Sept. 27, 2022

Sodium-glucose co-transporter 2 inhibitors (SGLT2-i) have shown significant cardiovascular benefits in patients with and without type diabetes mellitus (T2DM). They also gained interest for their potential anti-arrhythmic role ability to reduce the occurrence of atrial fibrillation (AF) ventricular arrhythmias (VAs) T2DM heart failure patients.To investigate in-hospital new-onset cardiac a cohort presenting acute myocardial infarction (AMI) treated SGLT2-i vs. other oral anti-diabetic agents (non-SGLT2-i users).Patients from SGLT2-I AMI PROTECT registry (NCT05261867) were stratified according use before admission AMI, divided into users non-SGLT2-i users. In-hospital outcomes included (NOCAs), defined as composite AF sustained tachycardia (VT) and/or (VF) during hospitalization.The study population comprised 646 categorized (111 patients) (535 patients). had lower rate NOCAs compared (6.3 15.7%, p = 0.010). Moreover, was associated VT/VF considered individually (p 0.032). In multivariate logistic regression model, after adjusting all confounding factors, identified an independent predictor (OR 0.35; 95%CI 0.14-0.86; 0.022). At multinomial regression, confounders, therapy remained 0.20; 0.04-0.97; 0.046) but not occurrence.In patients, risk arrhythmic events hospitalization AMI. particular, primary effect expressed reduction VAs. These findings emphasize cardioprotective effects setting beyond glycemic control.Data are part observational international registry: PROTECT. ClinicalTrials.gov, identifier: NCT05261867.

Language: Английский

Citations

62
Canagliflozin Improves Myocardial Perfusion, Fibrosis, and Function in a Swine Model of Chronic Myocardial Ischemia DOI
Sharif A. Sabe, Cynthia Xu, Mohamed Sabra

et al.

Journal of the American Heart Association, Journal Year: 2022, Volume and Issue: 12(1)

Published: Dec. 30, 2022

Background Sodium-glucose cotransporter-2 inhibitors are cardioprotective independent of glucose control, as demonstrated in animal models acute myocardial ischemia and clinical trials. The functional molecular mechanisms these benefits the setting chronic poorly defined. purpose this study is to determine effects canagliflozin therapy on perfusion, fibrosis, function a large model ischemia. Methods Results Yorkshire swine underwent placement an ameroid constrictor left circumflex artery induce Two weeks later, pigs received either no drug (n=8) or 300 mg sodium-glucose inhibitor orally, daily (n=8). Treatment continued for 5 weeks, followed by hemodynamic measurements, harvest, tissue analysis. Canagliflozin was associated with increased stroke volume work decreased ventricular stiffness compared controls. group had improved perfusion ischemic myocardium controls, without differences arteriolar capillary density. interstitial perivascular fibrosis chronically tissue, reduced Jak/STAT (Janus kinase/signal transducer activator transcription) signaling In group, there expression activation adenosine monophosphate-activated protein kinase, endothelial nitric oxide synthase, unchanged total synthase. oxidation mitochondrial antioxidant superoxide dismutase 2 Conclusions ischemia, improves territory, changes collateralization. Attenuation via signaling, may contribute effects.

Language: Английский

Citations

43
New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death DOI Open Access

Lan-Lan Bu,

Huanhuan Yuan,

Lingli Xie

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(20), P. 15160 - 15160

Published: Oct. 13, 2023

Endothelial cells (ECs) form the inner linings of blood vessels, and are directly exposed to endogenous hazard signals metabolites in circulatory system. The senescence death ECs not only adverse outcomes, but also causal contributors endothelial dysfunction, an early risk marker atherosclerosis. pathophysiological process EC involves both structural functional changes has been linked various factors, including oxidative stress, dysregulated cell cycle, hyperuricemia, vascular inflammation, aberrant metabolite sensing signaling. Multiple forms have documented atherosclerosis, autophagic death, apoptosis, pyroptosis, NETosis, necroptosis, ferroptosis. Despite this, molecular mechanisms underlying or atherogenesis fully understood. To provide a comprehensive update on subject, this review examines historic latest findings alterations associated with different stages

Language: Английский

Citations

42