Effect of SGLT-2 inhibitors on cardiac autonomic function in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials

Patoulias, Dimitrios; Katsimardou, Alexandra; Fragakis, Nikolaos; Papadopoulos, Christodoulos; Doumas, Michael

doi:10.1007/s00592-022-01958-0

Cited by 7 publications

(3 citation statements)

References 46 publications

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“…Dapagliflozin also ameliorated heart rate variability and heart rate turbulence parameters in patients with type 2 DM and CAN [ 141 ]. These findings contradict a recent meta-analysis that documented a trivial effect of SGLT2 inhibition on indices of CAN [ 142 ]. It should be noted that the improvement in CAN with SGLT2i may be more pronounced in individuals with HF, as suggested by the study of Hamaoka et al [ 143 ].…”

Section: A Novel Era In Heart Failure Pharmacotherapy: Sglt2 Inhibitorscontrasting

confidence: 99%

Diabetes Mellitus and Heart Failure: Epidemiology, Pathophysiologic Mechanisms, and the Role of SGLT2 Inhibitors

Theofilis

Oikonomou

Tsioufis

et al. 2023

Life

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Diabetes mellitus (DM) and heart failure (HF) are frequently encountered afflictions that are linked by a common pathophysiologic background. According to landmark studies, those conditions frequently coexist, and this interaction represents a poor prognostic indicator. Based on mechanistic studies, HF can be propagated by multiple pathophysiologic pathways, such as inflammation, oxidative stress, endothelial dysfunction, fibrosis, cardiac autonomic neuropathy, and alterations in substrate utilization. In this regard, DM may augment myocardial inflammation, fibrosis, autonomic dysfunction, and lipotoxicity. As the interaction between DM and HF appears critical, the new cornerstone in DM and HF treatment, sodium-glucose cotransporter-2 inhibitors (SGLT2i), may be able to revert the pathophysiology of those conditions and lead to beneficial HF outcomes. In this review, we aim to highlight the deleterious pathophysiologic interaction between DM and HF, as well as demonstrate the beneficial role of SGLT2i in this field.

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Section: A Novel Era In Heart Failure Pharmacotherapy: Sglt2 Inhibitorscontrasting

confidence: 99%

Diabetes Mellitus and Heart Failure: Epidemiology, Pathophysiologic Mechanisms, and the Role of SGLT2 Inhibitors

Theofilis

Oikonomou

Tsioufis

et al. 2023

Life

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“…Recent studies have linked cardiac autonomic neuropathy (CAN), a prevalent complication of T2DM, to coronary microvascular dysfunction. [32] T2DM may expedite the development of atherosclerosis, vascular alterations, and then further cause autonomic dysfunction. [33] In light of these findings, further longitudinal studies are needed to establish a cause-effect relationship between BP, ED, and autonomic vascular dysfunction among patients with T2DM.…”

Section: Discussionmentioning

confidence: 99%

Serum sclerostin level is positively associated with endothelial dysfunction measured by digital thermal monitoring in patients with type 2 diabetes: A prospective cross-sectional study

Hsu,

Wu,

Yang

et al. 2023

Medicine

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Sclerostin and dickkopf-1 (DKK1), extracellular inhibitors of the canonical Wnt/β-catenin signaling pathway, have been associated with vascular aging and atherosclerosis. This study aimed to assess the correlation of sclerostin and DKK1 concentrations with endothelial function measured using vascular reactivity index (VRI) in patients with type 2 diabetes mellitus (T2DM). Fasting blood samples were collected from 100 patients with T2DM. Endothelial function and VRI were measured using digital thermal monitoring and circulating sclerostin and DKK1 levels by enzyme-linked immunosorbent assays. VRI values < 1.0, 1.0–1.9, and > 2.0 indicated poor, intermediate, and good vascular reactivity, respectively. Overall, 30, 38, and 32 patients had poor, intermediate, and good vascular reactivity, respectively. Older age, higher serum glycated hemoglobulin, urinary albumin-to-creatinine ratio, and sclerostin as well as lower hypertension prevalence, systolic blood pressure, and diastolic blood pressure (DBP) were associated with poor VRI. Multivariable forward stepwise linear regression analysis showed that DBP (β = 0.294, adjusted R2 change = 0.098, P < .001), log-glycated hemoglobin (β = −0.235, adjusted R2 change = 0.050, P = .002), log-urine albumin-to-creatinine ratio (β = −0.342, adjusted R2 change = 0.227, P < .001), and log-sclerostin level (β = −0.327, adjusted R2 change = 0.101, P < .001) were independently associated with VRI. Serum sclerostin, along with glycated hemoglobin and albumin-to-creatinine ratio, exhibited a negative correlation with VRI, while DBP showed a positive correlation with VRI. These factors can independently predict endothelial dysfunction in patients with T2DM.

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“…Cardiac autonomic function was suggested as a major tool for risk stratification of patients with cardiovascular co-morbidities [76]. Some of us have recently documented, in a meta-analysis of all relevant RCTs, that SGLT-2 inhibitor treatment among patients with T2DM does not provide any significant benefit to cardiac autonomic function [77]. Remarkably, it has not been assessed whether SGLT-2 inhibitors affect cardiac autonomic function in the acute HF setting and the direct clinical implications, thus, future trials are required to shed further light on those major pathophysiologic mechanisms that have significant prognostic implications in this patients' population.…”

Section: Areas For Further Research and Concluding Remarksmentioning

confidence: 99%

The Therapeutic Role of SGLT-2 Inhibitors in Acute Heart Failure: From Pathophysiologic Mechanisms to Clinical Evidence with Pooled Analysis of Relevant Studies across Safety and Efficacy Endpoints of Interest

Patoulias

Rizzo

2022

Life

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(1) Background: Sodium-glucose co-transporter-2 (SGLT-2) inhibitors constitute a novel drug class with remarkable cardiovascular benefits for patients with chronic heart failure (HF). Recently, this class has been utilized in acute HF as an additional treatment option to classic diuretics, which remain the cornerstone of treatment. (2) Methods: We attempted to identify those pathophysiologic mechanisms targeted by SGLT-2 inhibitors, which could be of benefit to patients with acute HF. We then conducted a comprehensive review of the literature within the PubMed database in order to identify relevant studies, both randomized controlled trials (RCTs) and observational studies, assessing the safety and efficacy of SGLT-2 inhibitors in acute HF. (3) Results: SGLT-2 inhibitors induce significant osmotic diuresis and natriuresis, decrease interstitial fluid volume and blood pressure, improve left ventricular (LV) function, ameliorate LV remodeling and prevent atrial arrhythmia occurrence, mechanisms that seem to be beneficial in acute HF. However, currently available studies, including six RCTs and two real-world studies, provide conflicting results concerning the true efficacy of SGLT-2 inhibitors, including “hard” surrogate endpoints. (4) Conclusions: Current evidence appears insufficient to substantiate the use of SGLT-2 inhibitors in acute HF. Further trials are required to shed more light on this issue.

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Effect of SGLT-2 inhibitors on cardiac autonomic function in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials

Cited by 7 publications

References 46 publications

Diabetes Mellitus and Heart Failure: Epidemiology, Pathophysiologic Mechanisms, and the Role of SGLT2 Inhibitors

Diabetes Mellitus and Heart Failure: Epidemiology, Pathophysiologic Mechanisms, and the Role of SGLT2 Inhibitors

Serum sclerostin level is positively associated with endothelial dysfunction measured by digital thermal monitoring in patients with type 2 diabetes: A prospective cross-sectional study

The Therapeutic Role of SGLT-2 Inhibitors in Acute Heart Failure: From Pathophysiologic Mechanisms to Clinical Evidence with Pooled Analysis of Relevant Studies across Safety and Efficacy Endpoints of Interest

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