Cardiovascular Protection Research Articles

A Comprehensive Literature Review of Effect of Mineralocorticoid Receptor Blockers on Chronic Kidney Disease

Background: The literature surrounding the effects of mineralocorticoid receptor blockers on chronic kidney disease (CKD) has evolved significantly over recent years, reflecting a growing understanding of their potential benefits and risks. Literature Review: (Yanai et al., 2021) reinforced the cardiovascular protective effects of MRAs through their systematic review and meta-analysis, indicating that MRAs could significantly reduce cardiovascular events in CKD patients. In a similar vein, (B. Wish & Pergola, 2022) discussed the advantages of combining MRAs with ACE inhibitors or ARBs, while cautioning against the elevated risk of hyperkalemia. (Hu et al., 2023) provided a meta-analysis focusing on eplerenone, a selective MRA, suggesting its role as an adjunct therapy in CKD management, although they noted the need for further exploration of its safety profile. (Hedlund Møller et al., 2024) examined the paradoxical nature of MRA treatment, where increased hyperkalemia incidence was associated with decreased mortality risk, underscoring the need for a balanced approach in clinical decision-making. This duality illustrates the necessity of vigilant monitoring and patient management strategies to optimize the therapeutic benefits of MRAs while minimizing risks. Conclusion: In conclusion, the collective findings from these studies indicate that MRAs hold significant promise in the management of CKD, particularly in reducing proteinuria and offering cardiovascular protection. However, the associated risk of hyperkalemia poses a critical barrier to their widespread use. Future research is essential to further elucidate the long-term outcomes of MRA therapy, explore novel agents that separate organ protection from adverse effects, and establish guidelines that can enhance patient safety while maximizing therapeutic benefits.

A cost-utility analysis of adding SGLT2 inhibitors for the management of type 2 diabetes with chronic kidney disease in Thailand

Chronic kidney disease (CKD) in type 2 diabetes (T2D) patients is associated with end-stage renal disease and significant economic burden. While sodium glucose cotransporter-2 inhibitors (SGLT2i) show renal benefits in randomized controlled trials (RCTs), their cost-effectiveness in Thailand remains unclear. This study evaluates the cost-utility of adding SGLT2i (dapagliflozin, empagliflozin, and canagliflozin) to standard of care therapy (SoCT) for T2D patients with CKD in Thailand. A lifetime Markov model assessed economic and clinical outcomes. Data were derived from Thai studies, RCT subgroup analyses, and patient interviews. Sensitivity analysis was performed. Adding SGLT2i increased life expectancy (0.42-0.52 years) and QALYs (3.83- 3.91 vs. 3.50 with SoCT alone), but also increased lifetime costs ($1,275–$1,903). Empagliflozin was cost-effective at a WTP threshold of $4,336 per QALY ($3,386/QALY), while dapagliflozin ($5,783/QALY) and canagliflozin ($4,591/QALY) required price reductions. SGLT2i showed potential cost savings for dialysis and kidney transplantation compared to SoCT alone. Adding SGLT2i to SoCT for T2D and CKD patients increases costs but provides significant clinical benefits. Empagliflozin is cost-effective at a WTP threshold of $4,336/QALY, while dapagliflozin and canagliflozin require price reductions to be cost-effective. However, the analysis solely focuses on renal benefits, excluding other advantages like cardiovascular and heart failure protection.

The Role of SGLT-2 Inhibitors in Cardiovascular and Renal Protection

SGLT-2 inhibitors have revolutionized the management of chronic diseases, demonstrating profound cardiovascular and renal protective effects that extend beyond their original purpose of glucose-lowering in T2DM. These agents target fundamental pathophysiological mechanisms, including hemodynamic regulation, metabolic efficiency, inflammation, and oxidative stress, making them effective across diverse populations. Landmark clinical trials such as EMPA-REG OUTCOME, CANVAS, DAPA-HF, and DAPA-CKD have shown significant reductions in cardiovascular death, heart failure hospitalizations, and the progression of CKD, even in non-diabetic patients. While generally well-tolerated, SGLT-2 inhibitors require careful patient selection to mitigate risks such as euglycemic diabetic ketoacidosis and volume depletion. Their broad applicability underscores their role as a cornerstone therapy, redefining integrated care for heart failure, CKD, and related conditions. As research expands, SGLT-2 inhibitors promise to further transform chronic disease management, offering improved outcomes, quality of life, and survival for millions worldwide.

A Comprehensive Analysis of Diabetic Complications and Advances in Management Strategies

Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is a pervasive chronic disease that affects millions of people worldwide. It predisposes individuals to a range of severe microvascular and macrovascular complications, which drastically impact the patient's quality of life and increase mortality rates owing to various comorbidities. This extensive review explores the intricate pathophysiology underlying diabetic complications, focusing on key mechanisms, such as atherosclerosis, insulin resistance, chronic inflammation, and endothelial dysfunction. It also highlights recent therapeutic advancements, including the introduction of SGLT2 inhibitors and GLP-1 receptor agonists, which provide benefits beyond glycemic control and offer cardiovascular and renal protection. Furthermore, the future position of SGLT2 inhibitors and GLP-1 receptor agonists in terms of the prevention of diabetes and macrovascular diseases will be discussed. Considering the differences in insulin secretion capacity between Western and Asian patients, including Japanese patients, we propose a treatment strategy for high-quality diabetes in Japan.

The Impact of Polyphenols on Nutrition and Health

Polyphenols are plant-sourced compounds that exhibit important dietary features on human health. They have been defined and used either as a food source or as a raw material in the food industry to enhance functional properties and nutritional quality. They have significant positive bioactivities as; antioxidant, anti-inflammatory, anti-carcinogenic, cardiovascular health protection, immune supporter, and also benefits on digestion and brain functioning. The effects and bioactivity ranges were studied in the literature which has been discussed in the review to emphasize the importance of these natural compounds to provide insight into health and well-being.

[Gly14]-Humanin ameliorates high glucose-induced endothelial senescence via SIRT6

High glucose (HG) induced endothelial senescence is related to endothelial dysfunction and cardiovascular complications in diabetic patients. Humanin, a member of mitochondrial derived peptides (MDPs), is thought to contribute to aging-related cardiovascular protection. The goal of the study is to explore the pathogenesis of HG-induced endothelial senescence and potential anti-senescent effects of Humanin. Human umbilical vein endothelial cells (HUVECs) were exposed to glucose to induce senescence, determined by β-galactosidase staining and the expressions of p21, p53, and p16. A clinically relevant dose of HG (15 mM, HG) induced endothelial senescence after 72 h incubation without elevated apoptosis. HG-induced senescence was attributed to the induction of reactive oxygen species (ROS) caused by SIRT6 downregulation, as ROS inhibitor N-acetyl cysteine blocked HG-induced senescence, while inactivation of SIRT6 increased ROS levels and promoted senescence. Strikingly. pretreatment with [Gly14]-Humanin (HNG) antagonized the downregulation of SIRT6 in response to HG and alleviated ROS production and cell senescence. HG-induced reduction of SIRT6 results in ROS overproduction and endothelial senescence. Humanin protects against HG-induced endothelial senescence via SIRT6. This study provides new directions for biological products related to Humanin to be a potential candidate for the prevention of vascular aging in diabetes.

Effects and Impact of Selenium on Human Health, A Review.

Selenium (Se) is an essential trace element that is crucial for human health. As a key component of various enzymes and proteins, selenium primarily exerts its biological functions in the form of selenoproteins within the body. Currently, over 30 types of selenoproteins have been identified, with more than 20 of them containing selenocysteine residues. Among these, glutathione peroxidases (GPXs), thioredoxin reductases (TrxRs), and iodothyronine deiodinases (DIOs) have been widely studied. Selenium boasts numerous biological functions, including antioxidant properties, immune system enhancement, thyroid function regulation, anti-cancer effects, cardiovascular protection, reproductive capability improvement, and anti-inflammatory activity. Despite its critical importance to human health, the range between selenium's nutritional and toxic doses is very narrow. Insufficient daily selenium intake can lead to selenium deficiency, while excessive intake carries the risk of selenium toxicity. Therefore, selenium intake must be controlled within a relatively precise range. This article reviews the distribution and intake of selenium, as well as its absorption and metabolism mechanisms in the human body. It also explores the multiple biological functions and mechanisms of selenium in maintaining human health. The aim is to provide new insights and evidence for further elucidating the role of selenium and selenoproteins in health maintenance, as well as for future nutritional guidelines and public health policies.

The role of multimodality imaging in diabetic cardiomyopathy: a brief review

Diabetic cardiomyopathy (DMCM), defined as left ventricular dysfunction in the setting of diabetes mellitus without hypertension, coronary artery disease or valvular heart disease, is a well-recognized entity whose prevalence is certainly predicted to increase alongside the rising incidence and prevalence of diabetes mellitus. The pathophysiology of DMCM stems from hyperglycemia and insulin resistance, resulting in oxidative stress, inflammation, cardiomyocyte death, and fibrosis. These perturbations lead to left ventricular hypertrophy with associated impaired relaxation early in the course of the disease, and eventually culminating in combined systolic and diastolic heart failure. Echocardiography, cardiac nuclear imaging, and cardiac magnetic resonance imaging are crucial in the diagnosis and management of the structural and functional changes associated with DMCM. There appears to be a U-shaped relationship between glycemic control and mortality. Exogenous insulin therapy, while crucial, has been identified as an independent risk factor for worsening cardiovascular outcomes. On the other hand, Glucagon-like Peptide-1 Receptor Agonists and Sodium–Glucose Cotransporter 2 Inhibitors appear to potentially offer glycemic control and cardiovascular protection. In this review, we briefly discuss the pathophysiology, staging, role of multimodality imaging, and therapeutics in DMCM.

Histone Deacetylase Inhibitors as a Promising Treatment Against Myocardial Infarction: A Systematic Review.

Background/Objectives: Acute myocardial infarction (AMI) is a critical medical condition that requires immediate attention to minimise heart damage and improve survival rates. Early identification and prompt treatment are essential to save the patient's life. Currently, the treatment strategy focuses on restoring blood flow to the myocardium as quickly as possible. However, reperfusion activates several cellular cascades that contribute to organ dysfunction, resulting in the ischaemia/reperfusion (I/R) injury. The search for treatments against AMI and I/R injury is urgent due to the shortage of effective treatments at present. In this regard, histone deacetylase (HDAC) inhibitors emerge as a promising treatment against myocardial infarction. The objective of this systematic review is to analyse the effects of HDAC inhibitors on ventricular function, cardiac remodelling and infarct size, among other parameters, focusing on the signalling pathways that may mediate these cardiovascular effects and protect against AMI. Methods: Original experimental studies examining the effects of HDAC inhibitors on AMI were included in the review using the PubMed and Scopus databases. Non-experimental papers were excluded. The SYRCLE RoB tool was used to assess risk of bias and the results were summarised in a table and presented in sections according to the type of HDAC inhibitor used. Results: A total of 18 studies were included, 10 of them using trichostatin A (TSA) as an HDAC inhibitor and concluding that the treatment improved ventricular function, reduced infarct size, and inhibited myocardial hypertrophy and remodelling after AMI. Other HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA), valproic acid (VPA), mocetinostat, givinostat, entinostat, apicidin, and RGFP966, were also analysed, showing antioxidant and anti-inflammatory effects, an improvement in cardiac function and remodelling, and a decrease in apoptosis, among other effects. Conclusions: HDAC inhibitors constitute a significant promise for the treatment of AMI due to their diverse cardioprotective effects. However, high risk of selection, performance, and detection bias in the in vivo studies means that their application in the clinical setting is still a long way off and more research is needed to better understand their benefits and possible side effects.

Discovery of Non-Peptide GLP-1 Positive Allosteric Modulators from Natural Products: Virtual Screening, Molecular Dynamics, ADMET Profiling, Repurposing, and Chemical Scaffolds Identification.

Background/Objectives: Glucagon-like peptide-1 (GLP-1) receptor is currently one of the most explored targets exploited for the management of diabetes and obesity, with many aspects of its mechanisms behind cardiovascular protection yet to be fully elucidated. Research dedicated towards the development of oral GLP-1 therapy and non-peptide ligands with broader clinical applications is crucial towards unveiling the full therapeutic capacity of this potent class of medicines. Methods: This study describes the virtual screening of a natural product database consisting of 695,133 compounds for positive GLP-1 allosteric modulation. The database, obtained from the Coconut website, was filtered according to a set of physicochemical descriptors, then was shape screened against the crystal ligand conformation. This filtered database consisting of 26,325 compounds was used for virtual screening against the GLP-1 allosteric site. Results: The results identified ten best hits with the XP score ranging from -9.6 to -7.6 and MM-GBSA scores ranging from -50.8 to -32.4 and another 58 hits from docked pose filter and a second round of XP docking and MM-GBSA calculation followed by molecular dynamics. The analysis of results identified hits from various natural products (NPs) classes, to whom attributed antidiabetic and anti-obesity effects have been previously reported. The results also pointed to β-lactam antibiotics that may be evaluated in drug repurposing studies for off-target effects. The calculated ADMET properties for those hits revealed suitable profiles for further development in terms of bioavailability and toxicity. Conclusions: The current study identified several NPs as potential GLP-1 positive allosteric modulators and revealed common structural scaffolds including peptidomimetics, lactams, coumarins, and sulfonamides with peptidomimetics being the most prominent especially in indole and coumarin cores.

Generalizability of kidney and cardiovascular protection by finerenone to the real world in Italy: insights from Fidelio and Figaro studies.

We evaluated the proportion of Type 2 diabetes (T2D) patients with chronic kidney disease (CKD) participating in the AMD (Association of Medical Diabetologists) Annals initiative who met the eligibility criteria for phase III-studies on finerenone, showing its renal and cardiovascular benefits. This analysis involved all T2D patients seen in 2019 in 282 diabetes centers in Italy, for whom data on kidney function (estimated glomerular filtration rate and albuminuria) were available. Data are presented separately for different scenarios, covering the population with main eligibility criteria for inclusion in the FIDELIO-DKD and FIGARO-DKD trials. Among 343,037 T2D patients involved in the analysis, 5.4% met the eligibility criteria of the FIDELIO-DKD study (13.3% if we consider the population with fundus data) and 22.3% met those of the FIGARO-DKD trial. Overall, 110,000 (33%) patients were eligible for treatment with finerenone, with a male prevalence, an average age of 71years, and good control of the main risk factors (HbA1c 7.3%; BP 138/76mmHg; LDL-c 87mg/dl), albeit with large percentages of not well controlled patients (50% with SBP > 140mmHg; > 30% with LDL-c > 100mg/dl). Over 12% were on sodium/glucose cotransporter 2 inhibitors or glucagon-like peptide 1 receptor agonists. Based on the event rate from the FIDELITY pooled analysis, the number of potentially avoidable events was 21.7 per 1000 eligible patients for the cardiovascular composite outcome and 16.7 for the renal outcome. This analysis showed that approximately 33% of patients with T2D present the main eligibility criteria for treatment with finerenone and could therefore benefit from it in the near future.

Structural Elucidation and In Silico-Aided Toxicity Prediction of Forced Degradation Products of Ginsenoside Re Using Ultra-High-Performance Liquid Chromatography Equipped with a Diode Array Detector and Charged Aerosol Detector (UHPLC-DAD-CAD) and Liquid Chromatography Coupled to a High-Resolution Mass Detector (LC-HRMS).

Ginsenoside Re was the major bioactive component found rich in Panax ginseng C. A. Meyer, which exerted excellent cardiovascular protection, anti-inflammatory, and anti-oxidation effects. The generation of unexpected degradation products (DPs) may influence the therapeutic effect of Re, or even bring toxic effects to patients. However, to date, only a few reports were available about the stability of Re. The present study aims to systematically investigate the degradation behaviors of Re under different stress conditions, including hydrolysis (acidic, basic, and neutral), oxidation, humidity, thermal, and photolytic (ultraviolet and visible light) conditions. A total of thirteen DPs were putatively identified, and among them, nine were discovered for the first time in our study. The results showed that Re was sensitive to exposure to acidic, basic, and oxidation conditions. It underwent a series of chemical degradation reactions, including deglycosylation, dehydration, addition, oxidation at the double bond, and isomerization under various stress conditions. Structural characterization of these DPs was carried out by UHPLC-DAD-CAD and LC-LTQ/Orbitrap. A plausible mechanism of their formation was proposed to support the structures of all DPs of Re. In silico toxicity prediction and metabolism behavior assessment were done by Derek Nexus and Meteor Nexus software. Re and DP-1 to DP-6 were predicted to possess potential skin irritation/corrosion toxicity. DP-11 and DP-12 bear the potential for carcinogenicity, mutagenicity, irritation, hepatotoxicity, and skin sensitization. The observation of these DPs updates our knowledge regarding the stability of Re, which provides valuable information for quality control and to choose suitable storage conditions.

Long-Term Health Benefits of Breastfeeding: Obesity Prevention, Metabolic Health, and Cardiovascular Protection

Introduction: Recent research highlights a link between early dietary habits, especially breastfeeding, and reduced obesity risk in adulthood. Breastfeeding provides essential nutrients and compounds that may shape an infant’s metabolism. This article reviews current findings to guide parents in supporting lifelong healthy development. Material and Methods: This review examined 30 studies focusing on the relationship between breastfeeding and the risk of developing obesity. Relevant studies were identified through searches on PubMed and Google Scholar. Literature Analysis: The reviewed literature suggests a possible link between breastfeeding and a decreased likelihood of obesity in adulthood, although comprehensive, systematic research on this relationship is still scarce. Findings indicate that bioactive elements in breast milk and breastfeeding behaviors may play a role in early metabolic and appetite regulation, which could influence weight control later in life. Observational studies and case reports show varying impacts, often dependent on factors like the duration and exclusivity of breastfeeding, as well as broader environmental influences. Conclusions: Breastfeeding offers significant long-term health benefits, including reduced risks of obesity, type 2 diabetes, and cardiovascular diseases. Studies show that longer breastfeeding duration is associated with healthier weight trajectories, improved metabolic outcomes, and lower BMI and HDL levels later in life. Exclusive breastfeeding for six months or more provides substantial protection against obesity in childhood and adulthood. Early formula introduction is linked to higher BMI trajectories and increased metabolic risks. These findings emphasize the importance of promoting breastfeeding as a key public health strategy to support long-term health and disease prevention.

Unlocking the potential of glucagon-like peptide-1 receptor agonists in revolutionizing type 2 diabetes management: a comprehensive review.

Diabetes mellitus (DM) is a long-term metabolic disorder caused by inadequate production and resistance to insulin. The prevalence of DM is rapidly increasing, with type 2 diabetes (T2D) accounting for more than 90% of cases. Despite new treatments, many patients with T2D do not meet their glycemic targets due to clinical inertia. This review provides an overview of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) in the management of T2D. The review synthesizes data from clinical trials and meta-analyses on the efficacy, safety, and cost-effectiveness of GLP-1 RAs. It also discusses the mechanisms of action, classification, and barriers to adherence and persistence in therapy. GLP-1 RAs improve glycemic control by lowering A1C levels and promoting weight loss. They have cardioprotective effects and may reduce endothelial inflammation, oxidative stress, and blood pressure. Adherence to GLP-1 RAs is better with once-weekly injections, though gastrointestinal side effects and cost can affect persistence. Semaglutide and liraglutide have shown significant weight reduction, with semaglutide being particularly effective. GLP-1 RAs are cost-effective due to reduced healthcare costs associated with fewer hospitalizations and lower mortality rates. Safety concerns include gastrointestinal issues, pancreatitis, and rare cases of diabetic retinopathy and thyroid C-cell tumors. For clinical practice, GLP-1 RAs represent a valuable option not only for glycemic control but also for weight management and cardiovascular protection. Incorporating GLP-1 RAs into treatment plans can improve patient outcomes, and optimizing dosing regimens and addressing barriers such as cost and side effects are crucial to enhancing patient adherence and long-term treatment success.

Pharmacological activities and mechanisms of proteins and peptides derived from traditional Chinese medicine

Abstract Proteins and peptides are important active components of traditional Chinese medicine (TCM) widely found in plants, animals, and fungi. Modern research indicates that the protein constituents of TCM possess various pharmacological activities, including antitumor effect, immunomodulation, antioxidation, antihypertension, anti-inflammation, cardiovascular and nervous system protection, blood sugar regulation, and bacteriostasis effects. Despite significant progress in recent years regarding the pharmacological activities and mechanisms of TCM components, research on protein components of TCM has lagged. Many TCM protein components have yet to be effectively developed, and their pharmacological activities and mechanisms remain insufficiently elucidated. This article provides a comprehensive review of the pharmacological activities and mechanisms of TCM proteins and peptides. Additionally, the current shortcomings in research are discussed to offer some insights, aiming to promote further investigation of TCM proteins and peptides and facilitate their application in new drug development and clinical treatment.

Medicinal utility and cardiovascular protection of pomegranate or ginger in the treatment of diabetic/obese rats

Medicinal utility and cardiovascular protection of pomegranate or ginger in the treatment of diabetic/obese rats

Sex- and endurance training-mediated cardiovascular protection through lipids during exercise.

Premenopausal women and endurance-trained individuals of either sex have reduced cardiovascular disease (CVD) risk. Endurance training shifts fuel selection towards fats to spare carbohydrates; interestingly, women prioritize fats as an energy resource more than men do during exercise. Relying on fats during exercise drives whole-body lipolysis and promotes lipid uptake and oxidation capacity in skeletal muscles. These metabolic adaptations during exercise result in protection against diet-induced obesity, a healthy body fat distribution, and reduced plasma triacylglycerol (TG) concentrations. Here, we analyze how sex differences and endurance training mediate changes in skeletal muscles, including exercise-induced lipolysis, lipid uptake and β-oxidation, intramuscular TG storage, and postexercise lipid metabolism, and discuss how regulating this processes affects CVD risk.

VdCHS2 Overexpression Enhances Anthocyanin Biosynthesis, Modulates the Composition Ratio, and Increases Antioxidant Activity in Vitis davidii Cells.

Anthocyanins are significant secondary metabolites that are essential for plant growth and development, possessing properties such as antioxidant, anti-inflammatory, and anti-cancer activities and cardiovascular protection. They offer significant potential for applications in food, medicine, and cosmetics. However, since anthocyanins are mainly obtained through plant extraction and chemical synthesis, they encounter various challenges, including resource depletion, ecological harm, environmental pollution, and the risk of toxic residuals. To address these issues, this study proposes a plant cell factory approach as a novel alternative solution for anthocyanin acquisition. In this study, the VdCHS2 gene was successfully transformed into spine grape cells, obtaining a high-yield anthocyanin cell line designated as OE1. Investigations of the light spectrum demonstrated that white light promoted spine grape cell growth, while short-wavelength blue light significantly boosted anthocyanin production. Targeted metabolomics analysis revealed that the total anthocyanin content in the OE1 cell line reached 11 mg/g, representing a 60% increase compared to the WT. A total of 54 differentially accumulated metabolites were identified, among which 44 were upregulated. Overexpression of the CHS gene enhanced the expression of downstream genes involved in anthocyanin biosynthesis, resulting in the differential expression of CHI, F3Hb, F3'5'H, DFR4, and LDOX. This led to the differential accumulation of anthocyanin monomers, predominantly consisting of 3-O-glucosides and 3-O-galactosides, thereby causing alterations in anthocyanin levels and composition. Furthermore, the OE1 cell line increased the activity of various antioxidant enzymes, improved the clearance of reactive oxygen species, and reduced the levels of hydrogen peroxide (H2O2) and malondialdehyde (MDA). The subsequent cultivation of the transformed OE1 cell line, in conjunction with cell suspension culture, established a plant cell factory for anthocyanin production, significantly increasing anthocyanin yield while shortening the culture duration. This study elucidates the molecular mechanisms through which the VdCHS2 gene influenced anthocyanin accumulation and compositional variations. Additionally, it established a model for a small-scale anthocyanin plant cell factory, thereby providing a theoretical and practical foundation for the targeted synthesis of anthocyanin components and the development and utilization of plant natural products.

Glucagon-like Peptide Receptor Agonists (GLP-1 receptor agonists): A Powerful Addition to Foundational Therapy Kidney Care in Patients with Type 2 Diabetes Mellitus

There has been a veritable explosion in therapeutic options for patients with chronic kidney disease (CKD) and Type 2 diabetes mellitus (T2DM). For the past several decades, therapy for this condition has been limited to glycemic control, blood pressure control and utilization of angiotensin converting enzyme inhibitors (ACEi’s) or angiotensin 2 receptor blockers (ARBs). Recently, the emergence of therapies with organ protective effects has completely altered the landscape of therapy and outcomes for CKD in T2DM. Specifically, several large randomized clinical trials have demonstrated the positive impact of sodium glucose luminal transporter 2(SGLT2) inhibitors on the progression of kidney disease, end-stage kidney disease (ESKD), major adverse cardiovascular events (MACE), cardiovascular (CV) death, hospitalization for heart failure(HHF), all‑cause hospitalization, and all-cause mortality. Furthermore, finerenone, a non-steroidal mineralocorticoid receptor (nsMRA), has also been established as a component of foundational kidney therapy in patients with T2DM. A robust clinical trial program demonstrated kidney protection, CV protection and reductions in HHF in patients with CKD and T2DM. International guidelines have been updated to incorporate these agents as standards of care in this group of patients. CKD in T2DM is a complex disease and it stands to reason that multi‑targeted therapy could result in better outcomes for patients, similar to the management of patients with chronic heart failure. Those who follow this field will have noted that GLP-1 receptor agonists are listed as a component of guideline-directed management. However, these recommendations are based on the CV protective effect of these agents. Until recently, it was not clear if GLP‑1RA’s possessed kidney protective properties. The recent publication of the FLOW trial confirms that GLP-1 receptor agonists are, in fact, kidney protective.

GLP-1 receptor agonists in patients with chronic kidney disease and either overweight or obesity.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as game-changers across the cardiovascular-kidney-metabolic (CKM) spectrum: overweight/obesity, type 2 diabetes mellitus (T2DM) and associated chronic kidney disease (CKD) and cardiovascular disease (CVD). Liraglutide, semaglutide and tirzepatide are European Medicines Agency approved to improve metabolic control in T2DM and to decrease weight in persons with obesity [body mass index (BMI) ≥30kg/m2] or with overweight (BMI ≥27kg/m2) associated with weight-related comorbidities such as hypertension, dyslipidaemia, CVD and others. Additionally, liraglutide and semaglutide are approved to reduce CVD risk in patients with CVD and T2DM. Semaglutide is also approved to reduce CVD risk in patients with CVD and either obesity or overweight and in phase 3 clinical trials showed kidney and cardiovascular protection in patients with T2DM and albuminuric CKD (FLOW trial) as well as in persons without diabetes that had CVD and overweight/obesity (SELECT trial). Thus, nephrologists should consider prescribing GLP-1 RAs to improve metabolic control, reduce CVD risk or improve kidney outcomes in three scenarios: patients with overweight and a related comorbid condition such as hypertension, dyslipidaemia or CVD, patients with obesity and patients with T2DM. This review addresses the promising landscape of GLP-1 RAs to treat persons with overweight or obesity, with or without T2DM, within the context of CKD, assessing their safety and impact on weight, metabolic control, blood pressure and kidney and cardiovascular outcomes, as part of a holistic patient-centred approach to preserve CKM health.