The Effect of SGLT2 Inhibitor Dapagliflozin on Serum Levels of Apelin in T2DM Patients with Heart Failure

Abstract

Apelin is a multifunctional peptide that plays a pivotal role in cardiac remodeling and HF manifestation because of counteracting angiotensin-II. We hypothesized that positive influence of sodium-glucose co-transporter-2 (SGLT2) inhibitor on cardiac function in T2DM patients with HF might be mediated by apelin and that its levels seem to be a target of management. A total of 153 type 2 diabetes mellitus (T2DM) patients with II/III HF NYHA class and average left ventricular (LV) ejection fraction (EF) of 46% have been enrolled and treated with dapagliflosin. The serum levels of apelin and N-terminal brain natriuretic pro-peptide (NT-proBNP) were measured at baseline and over a 6-month period of dapagliflosin administration. We noticed that administration of dapagliflozin was associated with a significant increase in apelin levels of up to 18.3% and a decrease in NT-proBNP of up to 41.0%. Multivariate logistic regression showed that relative changes of LVEF, LA volume index, and early diastolic blood filling to longitudinal strain ratio were strongly associated with the levels of apelin, whereas NT-proBNP exhibited a borderline significance in this matter. In conclusion, dapagiflosin exerted a positive impact on echocardiographic parameters in close association with an increase in serum apelin levels, which could be a surrogate target for HF management.

Plausible prediction of renoprotective effects of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney diseases

“…Indeed, SGLT2 inhibitors demonstrated their ability to reduce the levels of hepcidin, inflammatory cytokines, such as IL-6, TNF-alpha, CRP and markers of kidney injury, as well as increase the levels of hemoglobin, erythropoietin, serum uric acid, adropin, irisin, and apelin. 19,22,28,34,44–48 The majority of these studies did not report any correlations between changes in the biomarkers of glomerular/tubular injury, altered glucose and lipid metabolism, adipocyte/skeletal muscle cell dysfunction and changes in UACR, whereas benefits in their changes were closely associated with slower decline in eGFR, for instance in the CREDENCE and DAPA-CKD trials. 19,28 Moreover, SGLT2 inhibitors seem to show improving kidney function independently of their glycemic effects, 49 while they are able to reduce tubular cell glucotoxicity via inhibition of sodium transporters, modulating mitochondrial dysfunction and suppressing local and systemic inflammatory reactions.…”

“…SGLT2 inhibitors have been suggested to prevent kidney fibrosis, podocyte injury and apoptosis of glomerular cells by increasing protective adipokine expression, such as adropin, irisin and apelin, which act directly through the activation of Akt/STAT3 and tyrosine protein kinase JAK2 (JAK2)/signal transducer pathways. 34,45,48,51,52 Finally, SGLT2 inhibitors adapt metabolic homeostasis by mediating the activity of NADPH oxidase and transcription factors (nuclear factor-κB and nuclear factor erythroid 2-related factor 2) preventing advanced glycation and autophagy. 51,52 These effects are considered to be crucial in the treatment of patients with either T2DM- or non-T2DM-related CKD who have HF.…”

SGLT2 inhibitor improves the prognosis of patients with coronary heart disease and prevents in-stent restenosis

“…Recently, dapagliflozin has also been shown to have a unique potential for cardioprotective effects by modulating apelin levels in patients and may serve as an alternative target for HF management in T2DM patients ( 99 ). Apelin is involved in the negative regulation of SMC proliferation and the improvement of EC function ( 100 , 101 ), but the specific mechanism is not clear.…”

Biomarkers in Heart Failure: From Research to Clinical Practice

“…Apelin and irisin seem to yield precise predictive information when added to NPs in patients with any HF phe-notype. Although the serial measures of these biomarkers appeared quite useful in terms of modification of HF management in patients with HFrEF, there are limited data supporting this finding [90,91].…”