Effect of SGLT2-Inhibitors on Epicardial Adipose Tissue: A Meta-Analysis

Masson, Walter; Lavalle-Cobo, Augusto; Nogueira, Juan Patricio

doi:10.3390/cells10082150

Cited by 55 publications

(39 citation statements)

References 49 publications

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“…In one study, dapagliflozin caused a reduction in EAT thickness independent of weight loss [215], perhaps thanks to the improvement of EAT cells' sensitivity to insulin and a reduction in local proinflammatory chemokines secretion [216]. Although SGLT2 inhibitors are relatively new drugs, the first meta-analyses have already confirmed their beneficial impact on EAT [217].…”

Section: Therapeutic Options To Affect Eatmentioning

confidence: 99%

“…Statins anti-inflammatory [160,[162][163][164][165] modulation of EAT [164] ↓ EAT metabolic activity [163] PCSK-9 inhibitors unknown Metformin anti-inflammatory [186,187,[196][197][198]200] ↑ fat oxidation and thermogenesis [193,194] ↓ endothelial dysfunction [195] activation of adenosine monophosphate-activated protein kinase [198,200] Thiazolidinediones anti-inflammatory [190,191,[204][205][206] SGLT2 inhibitors anti-inflammatory [210,217] ↓ endothelial dysfunction [213] stimulation of visceral fat burn [215] ↑ EAT cells sensitivity to insulin [217] GLP-1 agonists ↑ pre-adipocyte differentiation [225] ↑ thermogenesis [226] ↑ adipocyte browning [226] DPP-4 inhibitors anti-inflammatory [231][232][233] downregulation of the receptor for advanced glycation end-products [234] ↑ cyclic adenosine monophosphate/protein kinase A signaling and IL-6 production [235] ↓ ROS generation and intercellular adhesion molecule-1 expression [236] Table 1. Cont.…”

Section: Group Of Drugs Potential Mechanisms Of Actionmentioning

confidence: 99%

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Role of Epicardial Adipose Tissue in Cardiovascular Diseases: A Review

Konwerski

Opolski

Grabowski

et al. 2022

Biology

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Cardiovascular diseases (CVDs) are the leading causes of death worldwide. Epicardial adipose tissue (EAT) is defined as a fat depot localized between the myocardial surface and the visceral layer of the pericardium and is a type of visceral fat. EAT is one of the most important risk factors for atherosclerosis and cardiovascular events and a promising new therapeutic target in CVDs. In health conditions, EAT has a protective function, including protection against hypothermia or mechanical stress, providing myocardial energy supply from free fatty acid and release of adiponectin. In patients with obesity, metabolic syndrome, or diabetes mellitus, EAT becomes a deleterious tissue promoting the development of CVDs. Previously, we showed an adverse modulation of gene expression in pericoronary adipose tissue in patients with coronary artery disease (CAD). Here, we summarize the currently available evidence regarding the role of EAT in the development of CVDs, including CAD, heart failure, and atrial fibrillation. Due to the rapid development of the COVID-19 pandemic, we also discuss data regarding the association between EAT and the course of COVID-19. Finally, we present the potential therapeutic possibilities aiming at modifying EAT’s function. The development of novel therapies specifically targeting EAT could revolutionize the prognosis in CVDs.

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Section: Therapeutic Options To Affect Eatmentioning

confidence: 99%

Section: Group Of Drugs Potential Mechanisms Of Actionmentioning

confidence: 99%

Role of Epicardial Adipose Tissue in Cardiovascular Diseases: A Review

Konwerski

Opolski

Grabowski

et al. 2022

Biology

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“…Several possible hypotheses have been extensively discussed, including reductions in body weight, blood pressure, and heart failure incidence [20]. In previous studies, an SGLT2 inhibitor was shown to decrease the amount of pericardial fat and atrial fibrosis [22,23], which might attenuate the occurrence of atrial fibrillation. Several inflammatory cytokines were also revealed to be modified after SGLT2 inhibitor therapy [24,25], such as the NLRP3 inflammasome, which might reduce the area of cardiac fibrosis.…”

Section: Association Between Sglt2 Inhibitor Treatment and Atrial Fib...mentioning

confidence: 99%

“…For ischemic stroke and myocardial infarction, atherosclerosis of the artery is an important risk factor, and the amount of visceral fat has a significant association with atherosclerosis [29,30]. In previous studies, SGLT2 inhibitor therapy was proven to significantly decrease the amount of visceral fat [22,31]. In addition, SGLT2 inhibitors might also reduce adipose-mediated inflammation and proinflammatory cytokine production [32].…”

Section: Association Between Sglt2 Inhibitor Treatment and Other Card...mentioning

confidence: 99%

Clinical Observation of SGLT2 Inhibitor Therapy for Cardiac Arrhythmia and Related Cardiovascular Disease in Diabetic Patients with Controlled Hypertension

Jhuo

Lin

et al. 2022

JPM

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Sodium-glucose transporter 2 (SGLT2) inhibitors are new glucose-lowering agents that have been proven to be beneficial for patients with cardiovascular diseases, heart failure, and sudden cardiac death. However, the possible protective effects of cardiac arrhythmia have not yet been clarified in clinical practice. In this study, we attempted to demonstrate the effects of SGLT2 inhibitors on cardiac arrhythmia by medical records from a single center. This retrospective study included patients diagnosed with type 2 diabetes mellitus (DM) and controlled hypertension who prescribed the indicated glucose-lowering agents based on medical records from 2016 to 2019 from Kaohsiung Medical University Hospital. These patients were divided into two groups. Group one patients were defined as patients with SGLT2 inhibitor therapy, and group two patients were defined as patients without SGLT2 inhibitor therapy. Baseline characteristics were collected from medical records. Univariate, multivariate, and match-paired statistical analyses were performed for the study endpoints. The primary study outcome was the incidence of cardiac arrhythmias, including atrial and ventricular arrhythmias, after SGLT2 inhibitor therapy. The secondary study outcomes were the incidence of stroke, heart failure, and myocardial infarction after SGLT2 inhibitor therapy. From the initial 62,704 medical records, a total of 9609 people who met our experimental design criteria were included. The mean follow-up period was 51.50 ± 4.23 months. Group one included 3203 patients who received SGLT2 inhibitors for treatment, and group two included 6406 patients who received non-SGLT2 inhibitors for treatment. Multivariate analysis showed that group one patients had significantly lower incidences of total cardiac arrhythmia (hazard ratio (HR): 0.58, 95% confidence interval (CI): 0.38–0.89, p = 0.013) and atrial fibrillation (HR: 0.56, 95% CI: 0.35–0.88, p = 0.013) than those of group two patients. The secondary outcome analysis showed that group one patients also had a significantly lower risk of stroke (HR: 0.48, 95% CI: 0.33–0.7; p < 0.001), heart failure (HR: 0.54, 95% CI: 0.41–0.7, p < 0.001), and myocardial infarction (HR: 0.47, 95% CI: 0.31–0.72, p < 0.001). A time-to-event analysis showed that treatment of type 2 DM patients with SGLT2 inhibitors could reduce the probability of total cardiac arrhythmia and related cardiovascular disease, such as atrial fibrillation, stroke, heart failure, or myocardial infarction, by 0.5%~0.8%. This databank analysis showed that SGLT2 inhibitor therapy reduced the incidence of total cardiac arrhythmia and atrial fibrillation in type 2 DM patients and decreased the incidence of related cardiovascular diseases, such as stroke, heart failure, and myocardial infarction. However, additional investigations are needed to confirm this hypothesis.

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“…Of note, body weight loss following SGLT2i treatment has been associated with a lower risk of new-onset AF in patients with T2DM [110]. In addition, meta-analysis suggests that epicardial fat is significantly reduced in T2DM patients with SGLT2-i treatment [111]. While epicardial fat is known to promote AF or VF due to the activation of inflammasome and production of cytokines [38,39,112].…”

Section: Antiarrhythmic Efficacy Of Sglt2 Inhibitorsmentioning

confidence: 99%

Mechanisms Underlying Antiarrhythmic Properties of Cardioprotective Agents Impacting Inflammation and Oxidative Stress

Andelová

Bacova

Sýkora

et al. 2022

IJMS

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The prevention of cardiac life-threatening ventricular fibrillation and stroke-provoking atrial fibrillation remains a serious global clinical issue, with ongoing need for novel approaches. Numerous experimental and clinical studies suggest that oxidative stress and inflammation are deleterious to cardiovascular health, and can increase heart susceptibility to arrhythmias. It is quite interesting, however, that various cardio-protective compounds with antiarrhythmic properties are potent anti-oxidative and anti-inflammatory agents. These most likely target the pro-arrhythmia primary mechanisms. This review and literature-based analysis presents a realistic view of antiarrhythmic efficacy and the molecular mechanisms of current pharmaceuticals in clinical use. These include the sodium‑glucose cotransporter-2 inhibitors used in diabetes treatment, statins in dyslipidemia and naturally protective omega-3 fatty acids. This approach supports the hypothesis that prevention or attenuation of oxidative and inflammatory stress can abolish pro-arrhythmic factors and the development of an arrhythmia substrate. This could prove a powerful tool of reducing cardiac arrhythmia burden.

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Effect of SGLT2-Inhibitors on Epicardial Adipose Tissue: A Meta-Analysis

Cited by 55 publications

References 49 publications

Role of Epicardial Adipose Tissue in Cardiovascular Diseases: A Review

Role of Epicardial Adipose Tissue in Cardiovascular Diseases: A Review

Clinical Observation of SGLT2 Inhibitor Therapy for Cardiac Arrhythmia and Related Cardiovascular Disease in Diabetic Patients with Controlled Hypertension

Mechanisms Underlying Antiarrhythmic Properties of Cardioprotective Agents Impacting Inflammation and Oxidative Stress

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