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

Abstract

Heart failure with preserved ejection fraction (HFpEF) is a common clinical syndrome frequently seen in elderly patients, the incidence of which is steadily increasing due to an ageing population and the increasing incidence of diseases, such as diabetes, hypertension, obesity, chronic renal failure, and so on. It is a multifactorial disease with different phenotypic aspects that share left ventricular diastolic dysfunction, and is the cause of about 50% of hospitalizations for heart failure in the Western world. Due to the complexity of the disease, no specific therapies have been identified for a long time. Sodium-Glucose Co-Transporter 2 Inhibitors (SGLT2-Is) and Glucagon-Like Peptide Receptor Agonists (GLP-1 RAs) are antidiabetic drugs that have been shown to positively affect heart and kidney diseases. For SGLT2-Is, there are precise data on their potential benefits in heart failure with reduced ejection fraction (HFrEF) as well as in HFpEF; however, insufficient evidence is available for GLP-1 RAs. This review addresses the current knowledge on the cardiac effects and potential benefits of combined therapy with SGLT2-Is and GLP-1RAs in patients with HFpEF.

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

“…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 ].…”

Glucose variability: a new risk factor for cardiovascular disease

“…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.…”

Kidneys in heart failure: Impact of flozins

“…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.…”