Search Results (1,293)

Background: Chemokine CCL5 may drive inflammation and vascular risk in advanced liver disease, but its cardiovascular implications are unclear. Secreted by hepatic, endothelial, macrophage, and lymphocytic cells, CCL5 is involved in cytokine regulation. Its serum levels rise in acute liver injury and hepatocellular carcinoma (HCC), but decline with fibrosis progression in end-stage liver disease (ESLD). CCL5 has also been linked to atherosclerosis. This study aimed to evaluate serum CCL5 levels in ESLD patients listed for liver transplantation (LT) and to assess their potential role as markers of cardiovascular (CV) risk and portal hypertension. Methods: We conducted an observational cohort study. Between 2019 and 2022, patients with ESLD evaluated for LT were enrolled. Data on liver pathology, CV risk, and laboratory parameters were collected. Serum CCL5 concentrations were measured using Sigma Aldrich^® CCL5 ELISA kits (MilliporeSigma, St. Louis, MO, USA). The database was analyzed with IBM^® SPSS^® Statistics version 20 (Chicago, IL, USA). Results: Overall, 46 patients were included, 50% with viral hepatitis and 28.3% with alcohol-related liver disease. HCC was present in 37% of cases. The median CV risk scores (CAD_LT = 7, mCAD_LT = 7, CAR_OLT = 18) placed the population at moderate CV risk. Serum CCL5 levels did not vary significantly between viral vs. non-viral cirrhosis (5511.8 vs. 6272.5 pg/mL, p = 0.15) and were not influenced by the presence of HCC (6098.4 vs. 5771.3 pg/mL, p = 0.55). We did not detect a correlation with MELD score (p = 0.21) or CV risk scores (CAD_LT: p = 0.58; mCAD_LT: p = 0.70; CAR_OLT: p = 0.22). Patients with thrombocytopenia (<100,000/µL, 54.3%) or a history of esophageal variceal ligation had lower CCL5 levels (5170.9 vs. 6750.8 pg/mL, p = 0.002 and 4252.0 vs. 6237.5 pg/mL, p = 0.003, respectively). Similarly, patients with a history of previous variceal bleeding and spontaneous bacterial peritonitis (SBP) had lower levels of CCL5 (4373.8 vs. 6119.9 pg/mL, p = 0.02 and 3404.3 vs. 6606.7 pg/mL, p = 0.01, respectively). We found a negative correlation between CCL5 and QTc interval duration (τ = −0.216, p = 0.037), left ventricle size (LV: τ = −0.235, p = 0.027), and pulmonary artery pressure (RV/RA gradient: τ = −0.225, p = 0.03). CCL5 correlated positively with the inflammatory markers C-reactive protein (CRP) (τ = 0.246, p = 0.018) and fibrinogen (r = 0.216, p = 0.04). Conclusions: In liver transplant candidates, serum CCL5 is not associated with cardiovascular risk scores or coronary atherosclerotic burden, but is inversely associated with clinical markers of portal hypertension severity. These findings suggest that CCL5 may serve as a potential non-invasive surrogate marker of portal hypertension rather than a cardiovascular risk biomarker in ESLD. Full article

Carotid atherosclerosis remains one of the primary etiological factors underlying ischemic stroke, contributing to adult neurological disability and mortality. In recent years, non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression, actively modulating molecular pathways involved in atherogenesis. This systematic review, the first to be exclusively focused on carotid atherosclerosis, aimed at synthesizing current findings on the differential expression of ncRNAs throughout the natural history of the disease, thus providing the first comprehensive attempt to delineate a stage-specific ncRNA expression profile in carotid disease. A comprehensive literature search was conducted in PubMed and Scopus databases in January 2025, following PRISMA guidelines. Original studies involving human subjects with carotid atherosclerosis, evaluating the expression of intracellular or circulating ncRNAs, were included and then categorized according to their association with cardiovascular risk factors, carotid intima-media thickness (cIMT), presence of atherosclerotic plaques, plaque vulnerability, clinical symptoms, and ischemic stroke. Out of 148 articles initially identified, 49 met the inclusion criteria and were analyzed in depth. Among the different classes of ncRNAs, microRNAs (miRNAs) were the most frequently reported as dysregulated, followed by circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs). Notably, the majority of identified ncRNAs were implicated in key pathogenic mechanisms such as inflammatory signaling, vascular smooth muscle cell (VSMC) phenotypic modulation, and ABCA1-mediated cholesterol efflux. Collectively, the evidence underscores the association and possible involvement of ncRNAs in the initiation and progression of carotid atherosclerosis and its cerebrovascular complications. Their relative stability in biological fluids and cell-specific expression profiles highlight their strong potential as minimally invasive biomarkers and—possibly—novel therapeutic targets. Full article

Atherosclerosis remains a leading cause of cardiovascular mortality despite advances in pharmacological and interventional therapies. Current treatment approaches face limitations including systemic side effects, inadequate local drug delivery, and restenosis following vascular interventions. Gel-based technologies offer unique advantages through tunable mechanical properties, controlled degradation kinetics, high drug-loading capacity, and potential for stimuli-responsive therapeutic release. This review examines gel platforms across multiple scales and applications in atherosclerosis research and intervention. First, gel-based in vitro models are discussed. These include hydrogel matrices simulating plaque microenvironments, three-dimensional cellular culture platforms, and microfluidic organ-on-chip devices. These devices incorporate physiological flow to investigate disease mechanisms under controlled conditions. Second, therapeutic strategies are addressed through macroscopic gels for localized treatment. These encompass natural polymer-based, synthetic polymer-based, and composite formulations. Applications include stent coatings, adventitial injections, and catheter-delivered depots. Natural polymers often possess intrinsic biological activities including anti-inflammatory and immunomodulatory properties that may contribute to therapeutic effects. Third, nano- and microgels for systemic delivery are examined. These include polymer-based nanogels with stimuli-responsive drug release responding to oxidative stress, pH changes, and enzymatic activity characteristic of atherosclerotic lesions. Inorganic–organic composite nanogels incorporating paramagnetic contrast agents enable theranostic applications by combining therapy with imaging-guided treatment monitoring. Current challenges include manufacturing consistency, mechanical stability under physiological flow, long-term safety assessment, and regulatory pathway definition. Future opportunities are discussed in multi-functional integration, artificial intelligence-guided design, personalized formulations, and biomimetic approaches. Gel technologies demonstrate substantial potential to advance atherosclerosis management through improved spatial and temporal control over therapeutic interventions. Full article

Gene editing technologies have revolutionized therapeutic development, offering potentially curative and preventative strategies for cardiovascular disease (CVD), which remains a leading global cause of morbidity and mortality. This review provides an introduction to the state-of-the-art gene editing tools—including ZFNs, TALENs, CRISPR/Cas9 systems, base editors, and prime editors—and evaluates their application in lipid metabolic pathways central to CVD pathogenesis. Emphasis is placed on targets such as PCSK9, ANGPTL3, CETP, APOC3, ASGR1, LPA, and IDOL, supported by findings from human genetics, preclinical models, and recent first-in-human trials. Emerging delivery vehicles (AAVs, LNPs, lentivirus, virus-like particles) and their translational implications are discussed. The review highlights ongoing clinical trials employing liver-targeted in vivo editing modalities (LivGETx-CVD) and provides insights into challenges in delivery, off-target effects, genotoxicity, and immunogenicity. Collectively, this review captures the rapid progress of LivGETx-CVD from conceptual innovation to clinical application, and positions gene editing as a transformative, single-dose strategy with the potential to redefine prevention and long-term management of dyslipidemia and atherosclerotic cardiovascular disease. Full article

Background: High residual platelet reactivity (HRPR) and persistent dyslipidemia remain important unmet needs in cardiovascular risk management, particularly in patients undergoing coronary revascularization. Despite intensive lipid-lowering and antiplatelet therapy, a substantial proportion of patients fail to reach recommended low-density lipoprotein cholesterol (LDL-C) targets or exhibit inadequate platelet inhibition. Inclisiran, a PCSK9-targeting small interfering RNA, represents an emerging approach for long-term LDL-C reduction. Methods: A narrative review of the literature published between 2009 and 2025 was performed using PubMed, Scopus, Web of Science, and MEDLINE. Studies evaluating the addition of inclisiran to standard lipid-lowering therapy in patients with dyslipidemia and HRPR, assessed using the VerifyNow assay, were included. Illustrative clinical cases from Kazakhstan were analyzed to demonstrate real-world changes in LDL-C levels and platelet reactivity following insufficient response to conventional treatment. The review had a descriptive design. Results: Available evidence indicates that a significant proportion of high- and very-high-risk patients do not achieve LDL-C targets or are unable to tolerate high-intensity statin therapy. Inclisiran consistently induces sustained reductions in LDL-C and circulating PCSK9 levels. Emerging data suggest a potential indirect modulation of platelet reactivity associated with intensive lipid lowering. In patients at extreme cardiovascular risk—including those after coronary artery bypass grafting (CABG) and with long-standing multivessel coronary artery disease—inclisiran therapy was associated with marked LDL-C reduction and a trend toward normalization of platelet reactivity. Conclusions: Assessment of platelet function using the VerifyNow assay may improve identification of residual thrombotic risk in patients with advanced atherosclerotic disease. Inclisiran appears to be a promising adjunctive therapy for dyslipidemic patients with persistently elevated cardiovascular risk and HRPR despite standard treatment. Further prospective studies are warranted to clarify the relationship between intensive LDL-C lowering, platelet reactivity, and clinical outcomes, and to optimize integrated lipid-lowering and antiplatelet strategies. Full article

This work focuses on the development of a patient-specific transient CFD–FSI numerical model combined with the Time-Averaged Entropy Generation Rate (TAEGR) to predict hemodynamic parameters in the thoracic aorta, including the Oscillatory Shear Index (OSI) and the Time-Averaged Wall Shear Stress (TAWSS). While arterial blood flow can be modeled assuming either rigid or elastic arterial walls, the effect of wall compliance on these parameters, particularly on TAEGR, remains insufficiently characterized. Moreover, the interpretation of established indicators is not unique, as regions of vascular relevance may correspond to either high or low values of OSI and TAWSS. The proposed approach aims to identify symmetry and asymmetry in shear stress and entropy generation within the arterial wall, which are closely associated with the development of atherosclerotic plaque. Four aortas from clinical patients were analyzed using the proposed numerical framework to investigate blood flow behavior. The results revealed regions with high values of the hemodynamic parameters (OSI > 0.15, TAWSS ≥ 2 Pa, and TAEGR ≥ 20 $\mathrm{W}/{\mathrm{m}}^3\mathrm{K}$) predominantly located in the vicinity of the upper arterial branches. These regions, referred to as critical zones, are considered prone to the development of cardiovascular diseases, particularly atherosclerosis. The proposed numerical model provides a reliable qualitative framework for assessing symmetry and asymmetry in aortic blood flow patterns under different surgical conditions. Full article

Background: Cardiovascular risk models, such as the Framingham and atherosclerotic cardiovascular disease (ASCVD) calculators, have improved risk prediction but often fail to identify individuals who experience ASCVD events despite low or intermediate predicted risk. This suggests that underrecognized, non-traditional risk factors may contribute significantly to the development of atherosclerosis. Objective: This narrative review synthesizes and summarizes recent evidence on high-yield non-traditional risk factors for atherosclerosis, with a focus on clinically significant, emerging, and applicable contributors beyond conventional frameworks. This review is distinct in that it aggregates a wide array of non-traditional risk factors while also consolidating recent data on ASCVD in more vulnerable populations. Unlike the existing literature, this manuscript integrates in a single comprehensive review various domains of non-traditional atherosclerotic risk factors, including inflammatory, metabolic, behavioral, environmental, and physical pathways. An additional unique highlight in the same manuscript is the discussion of non-traditional risk factors for atherosclerosis in more vulnerable populations, specifically South Asians. We also focus on clinically actionable factors that can guide treatment decisions for clinicians. Results: Key non-traditional risk factors identified include inflammation and biomarker-based risk factors such as C-reactive protein or interleukin-6 levels, metabolic and microbial risk factors, behavioral factors such as E-cigarette use, and environmental or infectious risk factors such as air and noise pollution. We explore certain physical exam findings associated with atherosclerotic burden, such as Frank’s sign and Achilles tendon thickness. Conclusions: Atherosclerosis is a multifactorial process influenced by diverse and often overlooked factors. Integrating non-traditional risks into clinical assessment may improve early detection, guide prevention and personalize care. Future risk prediction models should incorporate molecular, behavioral, and environmental data to reflect the complex nature of cardiovascular disease. Full article

Background and Objectives: Obesity, heart failure (HF), and atherosclerosis have common pathways, including chronic inflammation, immune cells activation, and metabolic disturbances. These pathways often coexist and overlap, increasing cardiometabolic risk. Growth differentiation factor 15 (GDF-15) is an emerging cytokine linked to inflammation, oxidative stress, and metabolic dysregulation, which are common pathways between heart failure, obesity and atherosclerosis. Beyond its established prognostic value in cardiovascular diseases (CVD) and HF, recent evidence suggests that GDF-15 may also reflect subclinical atherosclerosis, potentially improving early risk stratification in obese and HF populations. The aim of this review is to synthesize current evidence on the association between GDF-15 and markers of subclinical atherosclerosis, and to evaluate whether GDF-15 may serve as an integrative biomarker reflecting shared cardiometabolic pathways. Materials and Methods: We conducted a systematic review following PRISMA recommendations registered by CRD420251267457 number on PROSPERO. PubMed, Embase, Scopus, and Web of Science were searched for human studies evaluating the correlation between markers of subclinical atherosclerosis and GDF-15 concentration. We excluded the studies not published in English, not involving human participants, and not meeting the inclusion criteria. We assessed the risk of bias using the Joanna Briggs Institute appraisal tool. Due to the heterogeneity of studies, a narrative synthesis was performed. Result: The review included 18 studies, which evaluated the association between GDF-15 and subclinical atherosclerosis markers, such as intima media thickness, coronary artery calcium score, ankle-brachial index, and atherosclerotic plaques. Studies included patients with metabolic disorders, chronic inflammatory diseases, HIV cohorts, and general population samples. Most of the studies reported that GDF-15 levels were associated with greater atherosclerotic burden; however, results were frequently influenced by confounders. Methodological limitations, such as limited or highly specified samples, cross-sectional designs, variability in atherosclerotic-imaging technique, and inconsistent adjustment for confounders, restrict generalization of the results. Conclusions: Current evidence supports GDF-15 as a biomarker integrating inflammatory and metabolic stress signals, indirectly linking obesity, HF and subclinical atherosclerosis. While current data supports its prognostic relevance, further studies are needed to confirm its clinical utility in routine assessment and preventive cardiovascular care. Full article

Current pharmacotherapies against atherosclerotic cardiovascular disease are associated with considerable residual risk, together with various adverse side effects. Nutraceuticals, such as resveratrol (RSV), with excellent safety profile, represent promising alternatives and potential treatment. However, the full spectrum of anti-atherogenic actions regulated by RSV and the underlying molecular mechanisms remain poorly understood. The objective of this study therefore was to investigate the impact of RSV on key atherosclerosis-associated processes in monocytes, macrophages, endothelial cells, and smooth muscle cells in vitro, as well as in LDL receptor-deficient mice fed a high-fat diet in vivo. RSV produced beneficial changes in the plasma lipid profile and peripheral blood lymphoid cells in vivo. RSV also attenuated plaque inflammation by decreasing macrophage and T cell content and enhanced markers of plaque stability, with increased levels of smooth muscle cells and collagen content. In vitro, RSV inhibited chemokine-driven monocyte migration, inflammasome activation, matrix metalloproteinase activity, pro-inflammatory gene expression, reactive oxygen species production, and smooth muscle cell invasion. RNA-sequencing of the thoracic aorta revealed key genes and pathways mediating the antioxidant, anti-inflammatory and plaque-stabilising activities of RSV. These studies provide novel mechanistic insights on the anti-atherogenic actions of RSV and support further evaluation in human clinical trials. Full article

Metformin, the most widely prescribed oral antihyperglycemic agent, is established as the first-line therapy for type 2 diabetes mellitus (T2DM) owing to its efficacy, affordability, and safety. Increasing evidence indicates that its benefits extend beyond glycemic control, encompassing cardiovascular protection and diabetes prevention in individuals at elevated cardiometabolic risk. Mechanistic studies demonstrate that metformin exerts pleiotropic effects through activation of AMP-activated protein kinase, modulation of the gut microbiota, inhibition of pro-inflammatory and oxidative stress pathways, and improvements in endothelial function, lipid metabolism, and insulin sensitivity. These actions address core drivers of atherosclerosis and metabolic dysfunction, many of which occur independently of glucose lowering. In patients with T2DM, the cardiovascular benefits of metformin are well recognized, including reductions in all-cause mortality and cardiovascular events. In individuals without diabetes but at high cardiovascular risk—such as those with prediabetes, obesity, or metabolic syndrome—evidence is more limited, as most data are derived from subgroup analyses or trials with surrogate endpoints. Nonetheless, consistent signals suggest that metformin may delay the progression from prediabetes to overt diabetes and potentially confer vascular protection, particularly in carefully selected high-risk populations. Clinical trials and meta-analyses have demonstrated that metformin reduces incident diabetes by approximately one quarter in high-risk adults, with stronger effects observed in younger, overweight individuals, women with prior gestational diabetes, and those treated for longer durations. However, uncertainties remain regarding its long-term cost-effectiveness, optimal dosing strategies, and cardiovascular benefits in non-diabetic populations. The ongoing VA-IMPACT trial (NCT02915198) is expected to clarify whether metformin reduces major cardiovascular events in prediabetic patients with atherosclerotic disease. Taken together, metformin represents more than an antidiabetic drug. Its pleiotropic mechanisms, favorable safety profile, and low cost support its potential integration into broader cardiometabolic prevention strategies, including primary prevention. Expanding its role beyond diabetes management may offer a cost-effective, widely accessible intervention with significant public health impact. Full article

Foam cell formation, a hallmark of early atherosclerotic lesion development, is closely associated with mitochondrial dysfunction and excessive reactive oxygen species (ROS) production. Disruption in mitochondrial activity leads to electron leakage, elevated ROS generation, and collapse of mitochondrial membrane potential, contributing to vascular pathogenesis. In this study, we investigated the role of Krüppel-like factor 2 (KLF2), a transcription factor known for its vasculoprotective effects, in regulating mitochondrial function during foam cell (FC) formation in RAW264.7 cells. This study demonstrates that KLF2 is decreased during FC formation of RAW264.7 cells. In contrast, lipids are highly uptaken, and both intracellular and mitochondrial ROS are increased, with enhanced mitochondrial membrane potential and mitochondrial functions during FC formation of RAW264.7 cells. To investigate the role of KLF2 in this FC formation process, we utilized both loss-of-function and gain-of-function approaches of KLF2 in RAW264.7 cells. This study demonstrates that KLF2 plays a multifaceted and protective role in preventing FC formation by regulating the uptake of lipids, reducing both intracellular and mitochondrial ROS, mitochondrial membrane potential, and mitochondrial activities, as loss-of-function of KLF2 promoted FC formation with overactivity, and gain-of-function reduced FC formation by limiting activities of all the parameters mentioned above. These findings provide mechanistic insights into the protective role of KLF2 and propose it as a potential therapeutic target for the future management of cardiovascular diseases. Full article

Background: Atherosclerosis (AS) serves as the primary pathological basis for cardiovascular disease-related deaths worldwide, posing a severe threat to public health security. Heat shock protein 90 (HSP90) plays a crucial regulatory role in the pathological progression of AS, emerging as a potential target for anti-atherosclerosis drug development in recent years. Calenduloside E (CE) is a pentacyclic triterpenoid saponin isolated from Aralia elata (Miq.) Seem. Previous studies have confirmed its anti-atherosclerotic activity, but its weak efficacy and narrow therapeutic index limit its clinical application. In this study, the CE scaffold was hybridized with a ticagrelor-derived fragment to enhance anti-atherosclerotic activity. In this study, the CE scaffold was hybridized with a ticagrelor fragment to achieve improved activity. Methods: Based on the principle of molecular hybridization, CE was linked to the active fragment of ticagrelor via a PEG chain. Ten CE derivatives were synthesized by modifying the sugar substituents. In vitro experiments were conducted to detect cytotoxicity and protective activity against ox-LDL-induced HUVECs injury. Molecular docking and Surface Plasmon Resonance (SPR) assays were used to evaluate the interaction between CE derivatives and the known target HSP90β. Combined with Microscale Thermophoresis (MST), SwissTargetPrediction, and molecular docking, other potential targets of CE derivatives were identified. Results: In the ox-LDL-induced HUVECs injury model, all compounds except C2 and C9 exhibited protective activity. Among these compounds, compound C5 exhibited the optimal protective effect, with an EC₅₀ value of 1.44 μM. Molecular docking results revealed that both C5 and CE could bind to HSP90β by forming hydrogen bonds with the key amino acid Asp93. Additionally, SPR results indicated that C5 and CE had similar binding affinities to HSP90β, with dissociation constants (K_D) of 1.73 μM and 1.72 μM, respectively. MST demonstrated that C5 binds to HSP90β with an affinity 111 times higher than that of ticagrelor. SwissTargetPrediction and molecular docking identified P2Y12 as another potential target of derivative C5. Conclusions: Compound C5 exerts protective effect against ox-LDL-induced HUVECs injury by targeting HSP90β. Its effective concentration is significantly improved compared with that of the parent CE, which provides a possibility for reducing clinical dosage and toxic side effects in subsequent studies. Furthermore, C5 may exert its effects by targeting another potential target, P2Y12, offering references for the rational design of novel anti-atherosclerotic drugs. Full article

Background/Objectives: Cardiovascular diseases are the leading cause of death worldwide. The preventive efforts to reduce the burden are crucial. Primary causes of cardiovascular diseases include lipid disorders. The variety of available medications influences cardiovascular risk and allows for improvement. However, discontinuation or infrequent initiation of lipid-lowering therapies remains a problem. This study aimed to investigate predictors of lipid-lowering therapy escalation. Methods: 431 patients with known concentrations of Lipoprotein (a) (Lp (a)) acquired as part of routine cardiovascular risk assessment from the HELPE-R registry, hospitalised in the University Clinical Hospital in Białystok were included in this study. Escalation of treatment was defined as the initiation of any form of lowering therapy or an increase in the potency or dose of statins. The analysis of the influence of various factors on the decision about escalation was performed. Results: The median age was 69.00 years. The escalation of therapy occurred in 48.49% of patients. Not reaching the LDL-C goal was the strongest predictor of escalation (OR: 9.177). The other factors increasing the probability of escalation included acute coronary syndrome (OR: 3.913), prediabetes (OR: 2.372), chronic coronary syndrome (OR: 2.217), dyslipidemia (OR: 2.354), hypertension (OR: 1.734), carotid artery stenosis (OR: 1.625), and obesity (OR: 1.543). There was no effect of past MI and stroke on the escalation of lipid profile. Lp (a) did not affect the escalation. Conclusions: The decision about escalation of lipid-lowering therapy is mainly influenced by classical risk factors and established atherosclerotic disease. Lp (a) did not affect the escalation, despite growing interest among medical practitioners. Full article

Low-density lipoprotein cholesterol (LDL-C) has traditionally been the primary biomarker used to assess cardiovascular risk. However, a substantial proportion of cardiovascular events occur in individuals with LDL-C levels within the normal range, highlighting the need for additional risk markers. Lipoprotein(a) [Lp(a)] has emerged as an independent and genetically determined cardiovascular risk factor that is not adequately captured by conventional lipid profiling. Elevated Lp(a) levels are associated with an increased risk of atherosclerotic cardiovascular disease, including coronary artery disease, ischemic stroke, and calcific aortic valve stenosis, and appear to be particularly relevant in the context of premature cardiovascular events. The pathogenicity of Lp(a) is driven by distinct mechanisms that extend beyond cholesterol transport. These include pro-atherogenic, pro-inflammatory, and pro-thrombotic effects mediated largely by oxidized phospholipids carried by the particle and by the structural properties of apolipoprotein(a), which interfere with fibrinolysis. Despite its strong and stable genetic determination, Lp(a) remains underrecognized and inconsistently measured in clinical practice, partly due to historical limitations in assay standardization and reporting. This minireview summarizes current knowledge on the pathophysiological mechanisms underlying elevated Lp(a), discusses its clinical implications for cardiovascular risk assessment, and highlights the importance of standardized Lp(a) measurement in routine practice, particularly in light of emerging Lp(a)-targeted therapies. Full article

Background/objectives: Chronic degenerative complications of diabetes, such as atherosclerotic cardiovascular disease and chronic kidney disease, contribute to an increased morbimortality in patients with type 2 diabetes (T2D), and thus, a multifactorial approach becomes essential. Among the classes of antihyperglycemic agents with beneficial pleiotropic cardiorenal effects, the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have proven to reduce the risk of major adverse cardiovascular (CV) and renal events. This study aims to assess the impact of treatment with GLP-1 RA on CV risk factors, insulin sensitivity, and renal function in Romanian patients with T2D. Methods: In an observational retrospective study, 150 patients with T2D were evaluated at the start of therapy with a GLP-1 RA and then after 6 and 12 months. Results: After 12 months of treatment, 59.3% of patients succeeded in achieving weight loss of over 5% of their initial weight, and 24.7% of patients achieved weight loss of over 10% of their initial weight, with the most significant decrease being measured in the first 6 months. HbA1c has shown a similar profile, with a significant reduction in the first 6 months of treatment, continued at a slower rate in the following 6 months. Additionally, the lipid profile, blood pressure values, and uric acid values, alongside the triglyceride/high-density lipoprotein cholesterol (TG/HDLc) ratio and the triglyceride–glucose (TyG) index have improved in these T2D patients treated with GLP-1 RA, while their eGFR decrease was slower than the one expected for similar populations without such a pharmacologic agent in their regimen. Conclusions: Treatment with GLP-1 RA in patients with T2D is associated with an improved cardiovascular–kidney–metabolic risk profile, ameliorated glycemic control, reduced weight, lower insulin resistance, and slower kidney disease progression. Full article