Endothelial Protection by Sodium-Glucose Cotransporter 2 Inhibitors: A Literature Review of In Vitro and In Vivo Studies

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(13), P. 7274 - 7274

Published: July 2, 2024

Endothelial dysfunction often precedes the development of cardiovascular diseases, including heart failure. The cardioprotective benefits sodium-glucose cotransporter 2 inhibitors (SGLT2is) could be explained by their favorable impact on endothelium. In this review, we summarize current knowledge direct in vitro effects SGLT2is endothelial cells, as well systematic observations preclinical models. Four putative mechanisms are explored: oxidative stress, nitric oxide (NO)-mediated pathways, inflammation, and cell survival proliferation. Both vivo studies suggest that share a class effect attenuating reactive oxygen species (ROS) enhancing NO bioavailability increasing synthase activity reducing scavenging ROS. Moreover, significantly suppress inflammation preventing expression adhesion receptors pro-inflammatory chemokines vivo, indicating another for protection. However, have not consistently shown regulation molecule SGLT2is. While improve under death-inducing stimuli, angiogenesis remains uncertain. Further experimental required to accurately determine interplay among these various complications, failure acute myocardial infarction.

Language: Английский

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Left ventricular remodeling response to SGLT2 inhibitors in heart failure: an updated meta-analysis of randomized controlled studies

Cardiovascular Diabetology, Journal Year: 2023, Volume and Issue: 22(1)

Published: Sept. 2, 2023

Abstract Background Randomized controlled trials (RCTs) reported contrasting results about reverse left ventricular remodeling (LVR) after sodium-glucose co-transporter-2 inhibitors (SGLT2i) therapy in patients with heart failure (HF). Methods and We performed a metanalysis of RCTs SGLT2i administration HF outpatients published until June 2022 searching four electronic databases. The protocol has been PROSPERO. Primary LVR outcome was change absolute LV end-diastolic (LVEDV) end-systolic volume (LVESV) from baseline to study endpoint. Secondary outcomes included changes LVEDV LVESV indexed body surface area, Mass index (LVMi), ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NTproBNP). Mean differences (MDs) 95% CIs were pooled. A total 9 (1385 patients) analyzed. All them data on LVEF. Six (n = 951); LVMi available 640. treatment significantly reduced [MD= -10.59 ml (-17.27; -3.91), P 0.0019], -8.80 (-16.91; -0.694), 0.0334], LVMI -5.34 gr/m2 (-9.76; -0.922), 0.0178], while LVEF increased [MD + 1.98% (0.67; 0.306), 0.0031]. By subgroup analysis, the beneficial effects did not differ by imaging method used, time follow-up re-evaluation, or phenotype. Reduction volumes tended be greater EF (HFrEF) than those preserved (HFpEF), opposite observed for LVMi. Conclusions Treatment reversed cardiac volumes, improving systolic function mass, particularly HFrEF patients.

Language: Английский

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Clinical features, treatment, and prognosis of SGLT2 inhibitors induced acute pancreatitis

Expert Opinion on Drug Safety, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 5

Published: Aug. 22, 2024

Background Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have recently been linked to be associated with acute pancreatitis (AP), but the clinical characteristics are unclear. This study investigated of SGLT-2i and AP provided reference for prevention treatment AP.

Language: Английский

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The therapeutic potential of ketones in cardiometabolic disease: impact on heart and skeletal muscle

AJP Cell Physiology, Journal Year: 2024, Volume and Issue: 326(2), P. C551 - C566

Published: Jan. 9, 2024

β-Hydroxybutyrate (βOHB) is the major ketone in body, and it recognized as a metabolic energy source an important signaling molecule. While oxidation essential brain during prolonged fasting/starvation, other organs such skeletal muscle heart also use ketones substrates. Additionally, βOHB-mediated molecular events occur cells, via metabolism and/or signaling, may contribute to optimal health cardiac function. Of importance, when of for ATP production molecules becomes disturbed presence underlying obesity, type 2 diabetes, cardiovascular diseases, these changes cardiometabolic disease. As result disturbances disease, multiple approaches have been used elevate circulating with goal optimizing either or ketone-mediated signaling. These produced significant improvements disease wide range benefits that include improved metabolism, weight loss, better glycemic control, vascular function, well reduced inflammation oxidative stress. Herein, we present evidence indicates therapy could be approach help treat diseases by targeting muscles.

Language: Английский

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Effect of empagliflozin on ventricular arrhythmias in patients with type 2 diabetes treated with an implantable cardioverter-defibrillator: the EMPA-ICD trial

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: June 28, 2024

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure and cardiovascular death with type diabetes; however, their effect on arrhythmias is unclear. The purpose this study was to investigate effects empagliflozin ventricular in patients diabetes. Methods A total 150 diabetes who were treated an implantable cardioverter-defibrillator or cardiac resynchronization therapy defibrillator (ICD/CRT-D) randomized once-daily placebo 24 weeks. primary endpoint change number from weeks before during treatment. Secondary endpoints included appropriate device discharges other values. Results In group, recorded by ICD/CRT-D decreased 1.69 treatment compared treatment, while increased 1.79. coefficient between-group difference − 1.07 (95% confidence interval [CI] 1.29 0.86; P < 0.001). 0.06 group 0.27 no significant between groups ( = 0.204). Empagliflozin associated increase blood ketones hematocrit a decrease brain natriuretic peptide body weight. Conclusions ICD/CRT-D, reduces placebo. Trial registration jRCTs031180120.

Language: Английский

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Effects of Glucagon‐Like Peptide‐1 Receptor Agonists, Sodium‐Glucose Cotransporter‐2 Inhibitors, and Their Combination on Neurohumoral and Mitochondrial Activation in Patients With Diabetes

Journal of the American Heart Association, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Background We investigated the effects of combined treatment with glucagon like peptide‐1 receptor agonists (GLP‐1RA) and sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2i) on NT‐proBNP (N‐terminal pro‐brain natriuretic peptide), GDF‐15 (growth differentiation factor 15), MOTS‐c (mitochondrial‐derived peptide‐c) in patients type 2 diabetes (T2D) high or very cardiovascular risk. Methods studied 163 consecutive who were treated insulin (n=40), liraglutide (n=41), empagliflozin (n=42), their combination (GLP‐1RA+SGLT‐2i) (n=40) matched using propensity score analysis. measured following at baseline 4 12 months treatment: (1) NT‐proBNP, GDF‐15, MOTS‐c; (2) 2,2′‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid), (3) left ventricular global longitudinal strain, atrial strain during reservoir phase, work index speckle‐tracking imaging. Results At months, GLP‐1RA, SGLT‐2i, showed a greater reduction (−43.1% versus −54.2% −56.9% −14.7%) than insulin. Only SGLT‐2i GLP‐1RA+SGLT‐2i improved MOTS‐c. provided an increase compared In all patients, was associated improvement index; decrease ABTS MOTs‐c constructive myocardial ( P <0.05). Conclusions Twelve‐month neurohumoral markers antioxidant ability each alone appear more effective mitochondrial activation. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03878706.

Language: Английский

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Ketone ester supplementation suppresses cardiac inflammation and improves cardiac energetics in a swine model of acute myocardial infarction

Metabolism, Journal Year: 2023, Volume and Issue: 145, P. 155608 - 155608

Published: June 1, 2023

Language: Английский

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The effect of SGLT2 inhibitors on the endothelium and the microcirculation: from bench to bedside and beyond

European Heart Journal - Cardiovascular Pharmacotherapy, Journal Year: 2023, Volume and Issue: 9(8), P. 741 - 757

Published: July 27, 2023

The beneficial cardiovascular effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors irrespective the presence diabetes mellitus are nowadays well established and they already constitute a significant pillar for management heart failure, ejection fraction. exact underlying mechanisms accountable these effects, however, remain largely unknown. direct effect on endothelial function microcirculation is one most studied. broad range studies presented in this review aims to link all available data from bench bedside highlight existing gaps as future directions investigations concerning SGLT2 endothelium microcirculation.An extensive search has been conducted using MEDLINE/PubMed database order identify relevant studies. Preclinical suggest that directly affect independently glucose specifically via several interplaying molecular pathways, resulting improved vasodilation, increased NO production, enhanced mitochondrial homeostasis, cell viability, angiogenesis attenuation oxidative stress inflammation. Clinical systematically confirm endothelium, whereas evidence conflicting.Preclinical clinical indicate attenuate microvascular dysfunction combination mechanisms, which play role their effect.

Language: Английский

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Ketone body levels and its associations with cardiac markers following an acute myocardial infarction: a post hoc analysis of the EMMY trial

Cardiovascular Diabetology, Journal Year: 2024, Volume and Issue: 23(1)

Published: April 27, 2024

Abstract Background Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been suggested to exert cardioprotective effects in patients with heart failure, possibly by improving the metabolism of ketone bodies myocardium. Methods This post hoc analysis EMMY trial investigated changes serum β-hydroxybutyrate (3-βOHB) levels after acute myocardial infarction (AMI) response 26-week Empagliflozin therapy compared usual post-MI treatment. In addition, association baseline and repeated measurements 3-βOHB cardiac parameters interaction were investigated. Cardiac included N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), ventricle end-systolic volume (LVESV), end-diastolic (LVEDV), filling pressure (E/é ratio). Results The mean increased from (46.2 ± 3.0 vs. 51.7 2.7) 6 weeks (48.8 2.2 42.0 2.3) 26 (49.3 35.8 1.9) group a consistent decline placebo over (p < 0.001). Baseline longitudinal not significantly associated NT-proBNP E/é ratio. value was negatively LVEF (coefficient: − 0.464, 95%CI 0.863;− 0.065, p = 0.023), while an increase its time positively (0.595, 0.156;1.035, 0.008). LVESV (1.409, 0.186;2.632, 0.024) LVEDV (0.640, 1.170;− 2.449, 0.488), these (LVESV: 2.099, 3.443;− 0.755, 0.002; LVEDV: 2.406, 4.341;− 0.472, 0.015). appears modify between 3-βOHB, 0.090), 0.134), 0.168), particularly at weeks; however, results statistically significant. Conclusion showed that SGLT2i AMI placebo. Higher inversely function follow-up, whereas sustained improved markers. highlights importance investigating body different phases. Although more pronounced effect on markers observed group, further research is required explore this effect.

Language: Английский

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Effect of empagliflozin in peripheral diabetic neuropathy of patients with type 2 diabetes mellitus

Medicina Clínica, Journal Year: 2024, Volume and Issue: 163(2), P. 53 - 61

Published: April 22, 2024

Language: Английский

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