Treatment of HFpEF beyond the SGLT2-Is: Does the Addition of GLP-1 RA Improve Cardiometabolic Risk and Outcomes in Diabetic Patients?

Belli, Martina; Barone, Lucy; Bellia, Alfonso; Sergi, Domenico; Lecis, Dalgisio; Prandi, Francesca Romana; Milite, Marialucia; Galluccio, Chiara; Muscoli, Saverio; Romeo, Francesco; Barillà, Francesco

doi:10.3390/ijms232314598

Cited by 15 publications

(9 citation statements)

References 130 publications

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“…Also, GLP1-RA have shown very promising results in clinical trials performed in diabetic and/or overweight patients. Future studies are needed to investigate and confirm the potential benefits of the association of these pharmacological classes, which may represent a novel intriguing therapeutic strategy [ 98 ].…”

Section: Discussionmentioning

confidence: 99%

Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium–Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure

Gallo,

Volpe

2024

IJMS

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Different multifactorial pathophysiological processes are involved in the development of heart failure (HF), including neurohormonal dysfunction, the hypertrophy of cardiomyocytes, interstitial fibrosis, microvascular endothelial inflammation, pro-thrombotic states, oxidative stress, decreased nitric oxide (NO) bioavailability, energetic dysfunction, epicardial coronary artery lesions, coronary microvascular rarefaction and, finally, cardiac remodeling. While different pharmacological strategies have shown significant cardiovascular benefits in HF with reduced ejection fraction (HFrEF), there is a residual unmet need to fill the gap in terms of knowledge of mechanisms and efficacy in the outcomes of neurohormonal agents in HF with preserved ejection fraction (HFpEF). Recently, type-2 sodium–glucose transporter inhibitors (SGLT2i) have been shown to contribute to a significant reduction in the composite outcome of HF hospitalizations and cardiovascular mortality across the entire spectrum of ejection fraction. Moreover, glucagon-like peptide-1 receptor agonists (GLP1-RA) have demonstrated significant benefits in patients with high cardiovascular risk, excess body weight or obesity and HF, in particular HFpEF. In this review, we will discuss the biological pathways potentially involved in the action of SGLT2i and GLP1-RA, which may explain their effective roles in the treatment of HF, as well as the potential implications of the use of these agents, also in combination therapies with neurohormonal agents, in the clinical practice.

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Section: Discussionmentioning

confidence: 99%

Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium–Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure

Gallo,

Volpe

2024

IJMS

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“…Ox-LDLs cause activation of endothelial cells, have cytotoxic effects on the endothelium and stimulate the production of several cell growth factors and adhesion molecules. Ox-LDLs also cause activation of several pro-inflammatory genes, increase platelet aggregation and thrombogenesis [ 38 ]. Taken together, all these mechanisms significantly contribute to the development and progression of atherosclerosis in patients with T2D.…”

Section: Pathogenesis Of Cardiovascular Complications In Diabetesmentioning

confidence: 99%

Glucose variability: a new risk factor for cardiovascular disease

et al. 2023

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Aims and data synthesis Glucose variability (GV) is increasingly considered an additional index of glycemic control. Growing evidence indicates that GV is associated with diabetic vascular complications, thus being a relevant point to address in diabetes management. GV can be measured using various parameters, but to date, a gold standard has not been identified. This underscores the need for further studies in this field also to identify the optimal treatment. Conclusions We reviewed the definition of GV, the pathogenetic mechanisms of atherosclerosis, and its relationship with diabetic complications.

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“…Several mechanisms explain the increased risk of CVD and HF in CKD patients. They include, among others: fluid overload and sodium retention, hypertension (which is likely to be resistant and require three or more antihyperten-sive drugs), increased activity of the renin-angiotensin-aldosterone system, increased sympathetic nervous system activity (with a special role of afferent sympathetic signaling from injured kidneys to the central nervous system as a contributing factor), systemic inflammation, endothelial dysfunction and many others [6,[26][27][28][29][30][31][32]. Although most of these mechanisms are not specific to CKD, they are more pronounced as compared with patients with preserved kidney function.…”

Section: Chronic Kidney Disease and Heart Failure: Modern Civilizatio...mentioning

confidence: 99%

Kidneys in heart failure: Impact of flozins

Stompór,

Winiarska

2023

Kardiol Pol

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Chronic kidney disease (CKD) and heart failure (HF) represent two modern diseases of civilization and are closely related. According to the concept of cardio-renal and reno-cardiac syndromes, most patients with CKD are affected by cardiovascular disease (CVD), and CVD (including HF) is one of the factors not only promoting progression of established CKD but also triggering its onset and development. Treatment of CVD and HF in CKD patients remains challenging since CKD patients are characterized by extremely diverse and strongly expressed risk profiles, and the data from well--designed clinical trials addressing this population are scarce. Nevertheless, it seems that most of the drugs used in the treatment of CVD and HF (including beta-blockers, angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor blocking agents, mineralocorticosteroid receptor antagonists, and sacubitril/valsartan) are of similar efficacy in patients with glomerular filtration rate (GFR) ranging between 45 and 60 ml/min/1.73 m 2 (although higher prevalence of side effects may limit their use). The data on cardiovascular (CV) drug efficacy in patients with lower GFR values (i.e., below 30-45 ml/min/1.73 m 2 ) remain limited. In this review, we focused on the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in the treatment of CVD and HF in CKD patients with or without diabetes. SGLT2i are clearly cardioprotective in a wide spectrum of estimated GFR although the data for HF patients with respect to urine albumin-creatinine ratio (UACR) are scarce, and for those with significantly reduced estimated GFR are still not available or not convincing, even after completion of large-scale high-quality major cardiovascular outcome trials (CVOT) in type 2 diabetes mellitus (T2DM) or trials with flozins in CKD and HF.

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Treatment of HFpEF beyond the SGLT2-Is: Does the Addition of GLP-1 RA Improve Cardiometabolic Risk and Outcomes in Diabetic Patients?

Cited by 15 publications

References 130 publications

Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium–Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure

Potential Mechanisms of the Protective Effects of the Cardiometabolic Drugs Type-2 Sodium–Glucose Transporter Inhibitors and Glucagon-like Peptide-1 Receptor Agonists in Heart Failure

Glucose variability: a new risk factor for cardiovascular disease

Kidneys in heart failure: Impact of flozins

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