Search Results (234)

Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) coexist in 40–60% of cases and mutually reinforce each other through adverse electrical, cellular, and functional remodelling. There is considerable overlap in signs and symptoms, and diagnosis may be challenging due to nonspecific clinical presentations and chronic course. AF is clearly linked with worsening morbidity and mortality in HFpEF with higher rates of HF hospitalizations, HF progression, stroke, systemic embolism, and all-cause death. Optimal management of HFpEF-AF patients requires aggressive treatment of comorbidities and risk factor modification. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated consistent benefit with respect to HF hospitalizations, symptoms and exercise haemodynamics, and potential to reduce AF burden. Gastric inhibitory polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) agonists, mineralocorticoid receptor antagonists (MRAs), angiotensin receptor-neprilysin inhibitors (ARNIs), and statins may provide benefit in selected phenotypes, though evidence remains heterogeneous. A rhythm control strategy in the early clinical course of HFpEF might be a reasonable strategy to improve symptoms and delay both AF and HFpEF disease progression. Catheter ablation appears to improve exercise haemodynamics and quality of life, and observational data suggest it may reduce mortality and HF hospitalization, though current evidence is inconsistent and not yet definitive. Emerging device-based and molecular therapies could represent promising avenues for future research. Overall, early detection of AF, comprehensive risk-factor modification, and tailored rhythm-control strategies are central to improving outcomes in the HFpEF-AF overlap syndrome. Full article

Background and Objectives: Patients with type 2 diabetes mellitus (T2DM) and ischemic stroke present with endothelial, vascular and left ventricular (LV) myocardial dysfunction. We investigated the effects of treatment with either glucagon-like peptide-1 receptor agonists (GLP-1RA) or sodium-glucose contrasporter-2 inhibitors (SGLT-2i) on endothelial glycocalyx, arterial stiffness, and LV myocardial strain in patients with metformin-treated T2DM and a prior ischemic stroke. Materials and Methods: A total of 54 consecutive patients with T2DM and ischemic stroke who attended a cardiometabolic outpatient clinic in Athens, Greece, and received either GLP-1RA (dulaglutide; n = 27) or SGLT-2i (empagliflozin; n = 27) were enrolled in the study. We measured the perfused boundary region (PBR) of the sublingual microvessels, a marker of glycocalyx thickness, as well as carotid-femoral pulse wave velocity (PWV) and LV global longitudinal strain (GLS), at baseline and at 4 and 12 months of treatment. Results: Twelve months after treatment, all patients had reduced glycosylated hemoglobin and body mass index (BMI) (p < 0.001). Patients treated with dulaglutide showed a greater reduction in BMI (−11.8% vs. −4.8%, p < 0.001) compared to those treated with empagliflozin. Compared to baseline, all patients had reduced PBR, PWV and GLS (p < 0.001) after 12 months of treatment. However, empagliflozin presented a greater decrease in PWV (−14% vs. −10.9%, p = 0.041), while dulaglutide resulted in a greater increase in GLS (14.7% vs. 8.3%, p = 0.024) compared to empagliflozin. In all patients, the reduction in PBR at 12 months was correlated with a decrease in PWV and with an increase in GLS (p < 0.05). Conclusions: Both dulaglutide and empagliflozin improve cardiovascular function in T2DM patients with ischemic stroke. Dulaglutide appears to be more effective in the improvement of LV myocardial strain, whereas empagliflozin is more effective in reducing arterial stiffness. Full article

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter-2 (SGLT2) inhibitors have reshaped pharmacological management of type 2 diabetes, but emerging safety signals suggest a possible association with intestinal obstruction. Because many candidates for these agents already harbor risk factors for ileus and bowel obstruction, clarifying agent- and dose-specific gastrointestinal safety is clinically important. We aimed to re-evaluate the risk of intestinal obstruction across individual GLP-1 receptor agonists and SGLT2 inhibitors, with particular attention to dose stratification. We systematically searched eight databases through 21 January 2025 to identify randomized controlled trials (RCTs) comparing GLP-1 receptor agonists or SGLT2 inhibitors with placebo or active comparators in adults. The primary outcome was incident intestinal obstruction (small or large bowel). A frequentist random-effects network meta-analysis estimated odds ratios (ORs) with 95% confidence intervals (CIs) across drugs and dose tiers; Bayesian models and surface under the cumulative ranking (SUCRA) metrics were used for sensitivity analyses and treatment ranking. Risk of bias and certainty of evidence were assessed with standard Cochrane and GRADE-adapted tools. Fifty RCTs (47 publications; 192,359 participants) met inclusion criteria. Overall, canagliflozin use was associated with a higher incidence of intestinal obstruction than control therapies (OR 2.56, 95% CI 1.01–6.49), corresponding to an absolute risk difference of 0.15% and a number needed to harm of 658. High-dose canagliflozin (300 mg/day) showed the clearest signal (OR 3.42, 95% CI 1.08–10.76). In contrast, liraglutide was associated with a lower risk of intestinal obstruction (OR 0.44, 95% CI 0.24–0.81), with an absolute risk reduction of 0.34% and a number needed to treat of 295. No other GLP-1 receptor agonist or SGLT2 inhibitor demonstrated a statistically significant increase in obstruction risk. Frequentist and Bayesian analyses yielded concordant estimates and rankings. From a randomized-trial perspective, intestinal obstruction risk is not elevated for most GLP-1 receptor agonists and SGLT2 inhibitors. A dose-dependent safety signal was observed only for high-dose canagliflozin, whereas liraglutide may confer a protective effect. These findings refine gastrointestinal safety profiles for modern antidiabetic agents and may inform perioperative bowel management, drug selection, and dose optimization in patients at risk for ileus or adhesive obstruction. Full article

Background: Despite the lack of formal indication for glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) in post-transplant diabetes mellitus (PTDM), their use in clinical practice is growing. While robust evidence supporting their use in kidney transplant recipients (KTRs) remains limited, PTDM remains a major driver of adverse outcomes, including cardiovascular morbidity, accelerated graft dysfunction, graft loss, and reduced survival. Methods: This retrospective cohort study analyzed adult KTRs with PTDM treated with SGLT2is and/or GLP-1 RAs between 2013 and 2024. Metabolic, kidney, and safety parameters were assessed from baseline to follow-up. Results: After a median treatment duration of 1.8 years, glycated hemoglobin (HbA1c) changed from 7.22% to 7.01% (p = 0.558), whereas fasting plasma glucose increased from 112.62 mg/dL to 125.01 mg/dL (p = 0.03). Body mass index decreased from 27.27 kg/m² to 25.95 kg/m² (p < 0.001). The lipid profile improved, with reductions in total cholesterol (p < 0.01) and low-density lipoprotein cholesterol (LDL-c, p = 0.02). Kidney function remained stable throughout the observation period, and adverse events were infrequent. Conclusions: In KTRs with PTDM, GLP-1 RAs and SGLT2is were associated with significant improvements in weight and lipid metabolism, alongside stable kidney function and a favorable safety profile. These findings support the consideration of these agents in the management of PTDM. Prospective studies are warranted to confirm these results. Full article

Background/Objectives: Diabetes mellitus (DM) represents a major global public health challenge and is consistently associated with an increased risk of atrial fibrillation (AF). Despite extensive epidemiological evidence linking the two conditions, the underlying mechanisms and the influence of glucose-lowering therapies on AF susceptibility remain incompletely defined. This review aims to summarize the current knowledge on the pathophysiological pathways linking DM and AF and to assess the impact of commonly used antidiabetic therapies on arrhythmic risk. We conducted a narrative review of epidemiological studies, mechanistic research, and cardiovascular outcome trials that evaluate the association between DM and AF. We included data addressing structural, electrical, autonomic, metabolic, and inflammatory mechanisms of AF in diabetes, as well as clinical evidence regarding the impact of metformin, insulin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium–glucose cotransporter-2 (SGLT-2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists on AF incidence or recurrence. Results: DM promotes AF development through multiple complementary mechanisms, including atrial fibrosis, electrical conduction abnormalities, autonomic dysfunction, inflammation, glycemic fluctuations, oxidative stress, and expansion of epicardial adipose tissue. These changes create a vulnerable atrial substrate that facilitates both initiation and maintenance of AF. Evidence from recent trials indicates that the arrhythmic effects of glucose-lowering therapies are heterogeneous. Metformin and SGLT-2 inhibitors appear to offer favorable or neutral effects on AF risk. GLP-1 receptor agonists provide substantial cardiovascular benefits, although their specific impact on AF remains under investigation. Insulin therapy has been linked to a higher AF risk, whereas DPP-4 inhibitors show an overall neutral effect with inconsistent findings across studies. Conclusions: AF in patients with DM results from complex interactions between metabolic disturbances, structural remodeling, and inflammatory activation. Although several antidiabetic drugs appear to have potential antiarrhythmic effects, further dedicated research is needed to clarify their role in AF prevention and management. Full article

Diabetes mellitus (DM) continues to be a global world health problem. Despite medical advances, both DM and chronic kidney disease (CKD) remain global health issues with high mortality and limited options to prevent end-stage renal failure. Current therapies encompass five classes of drugs: (1) angiotensin-converting-enzyme inhibitors (ACEI) or angiotensin II receptor blockers (AIIRB); (2) sodium-glucose-transporter 2 (SGLT2) inhibitors; (3) glucagon-like peptide-1 receptor agonists (GLP-1 RA); and (4) an antagonist of type 1 endothelin receptor (ET1R) with proven efficacy to reduce albuminuria and proteinuria. (5) The mineralocorticoid receptor antagonist (MRA) finerenone has been tested in RCTs as a kidney protective agent. In our review, we summarize many of the principal trials that have generated evidence in this regard. Many novel agents—many of them proven not only for DM management but also for the treatment of obesity with or without DM or heart failure (HF)—are now in development and may be added to the five classical pillars: other non-steroidal MRA (balcinrenone); aldosterone synthase inhibitors (baxdrostat and vicadrostat); other GLP-1 RA (tirzepatide, survodutide, retatrutide, and cagrilintide); ET1 R antagonists, (zibotentan); and soluble guanylate cyclase activators (avenciguat). These new agents aim to slow disease progression further and reduce cardiovascular risk. Future strategies rely on integrated, patient-centered approaches and personalized therapy to curb renal disease and its related complications. Full article

Background/Objectives: Recent randomized controlled trial evidence in adults with type 2 diabetes (T2D) and chronic kidney disease (CKD) indicates that adding finerenone to empagliflozin provides additive clinical benefit. A prespecified analysis demonstrates that this benefit is consistent irrespective of prior glucagon-like peptide-1 receptor agonist (GLP-1 RA) use. We aimed to assess the effectiveness of adding finerenone to existing sodium-glucose cotransporter-2 inhibitor (SGLT2i) and GLP-1 RA therapy in a real-world setting. Methods: We performed a retrospective cohort study of adults with T2D and CKD from Maccabi Healthcare Services diabetes, endocrinology, and nephrology clinics in Haifa, Israel. Included individuals initiated finerenone between 1 August 2023, and 31 January 2025, and met the following criteria: estimated glomerular filtration rate (eGFR) of 25–60 mL/min/1.73 m²; urinary albumin-to-creatinine ratio (UACR) > 300 mg/g; and a history of ≥12 weeks of SGLT2i (empagliflozin or dapagliflozin) and GLP-1 RA (liraglutide, dulaglutide, or semaglutide) use prior to finerenone initiation. Outcomes were assessed at the last measurement taken within 26 ± 10 weeks of finerenone initiation. The primary outcome was adjusted percent change in log-transformed UACR from baseline to follow-up. Secondary outcomes were adjusted mean changes in eGFR and serum potassium. We used multiple linear regression models. Prespecified subgroup analyses examined the UACR change by age, sex, body mass index (BMI), baseline eGFR, and baseline UACR. Results: Fifty-one individuals were included in the study, with a mean age of 66.0 ± 9.5 years and a mean BMI 30.9 ± 5.2 kg/m². The median eGFR was 45 mL/min/1.73 m² (IQR 36–52), and the median UACR was 1001 mg/g (IQR 515–1599). 94% were receiving a renin–angiotensin system inhibitor. Finerenone was initiated at 10 mg/day and titrated to 20 mg/day in eight individuals. Over a median follow-up of 27 weeks, the adjusted percent change in UACR was −51.3% (p < 0.001), consistent across prespecified subgroups. The adjusted mean eGFR change was −3.92 mL/min/1.73 m² (p < 0.001). Serum potassium increased by +0.34 mmol/L (p < 0.001). Conclusions: In adults with T2D and albuminuric CKD already receiving an SGLT2i and a GLP-1 RA, adding finerenone substantially reduced albuminuria. Full article

Background: Although glucagon-like peptide-1 (GLP-1) receptor agonists and sodium–glucose cotransporter 2 (SGLT2) inhibitors have gained attention for their broad therapeutic effects, their influence on hematologic malignancy remains underexplored. Given the high mortality associated with hematologic cancers, clarifying the impact of these agents on such malignancies is essential. Objectives: This pilot network meta-analysis (NMA) aimed to assess the comparative risk of hematologic malignancies—including lymphoma, leukemia, and myeloma—associated with various GLP-1 receptor agonists and SGLT2 inhibitors. Methods: Following Cochrane-recommended confirmatory methods, we systematically searched multiple databases for randomized controlled trials (RCTs) published through 4 December 2024. The primary outcome was the incidence of overall hematologic malignancies. A frequentist random-effects NMA via the netmeta package was conducted, with additional validation through Bayesian NMA for solely sensitivity analyses. Results: Fifty-five RCTs (n = 200,606) were analyzed. Dulaglutide showed a significantly higher risk of overall hematologic malignancy [odds ratio (OR) = 2.18, 95% confidence interval (95%CI) = 1.14–4.19). In contrast, tirzepatide was linked to a significantly reduced risk (OR = 0.14, 95%CI = 0.03–0.60), especially for lymphoma. No statistically significant associations were identified for SGLT2 inhibitors (i.e., 95%CI across 1.0). Conclusions: Our preliminary findings reveal distinct and agent-specific effects of GLP-1 receptor agonists on hematologic malignancy risk. While dulaglutide may elevate the risk, tirzepatide appears protective, particularly against lymphoma. These results call for further long-term mechanistic studies to clarify causality and underlying pathways. Full article

Obesity is a complex, multifactorial disease wherein the excessive accumulation of adipose tissue leads to adverse health outcomes, such as diabetes, cardiovascular disease and musculoskeletal disorders. Obesity also impacts both the risk and the clinical prognosis of heart failure (HF). The accumulation of adipose tissue results in metabolic dysregulation, including increased levels of pro-inflammatory cytokines and adipokines. These alterations are strongly associated with the development and progression of HF. Another significant comorbidity in patients with HF is sarcopenia, characterized by progressive loss of muscle mass and strength, affecting the quality of life. The study aims to critically synthesize the mechanisms by which modern pharmacological treatments—sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dual GIPR/GLP-1R agonists—modulate body mass composition, and to analyze the specific implications of these changes (e.g., visceral fat reduction versus lean mass loss) for heart failure (HF) prognosis and management. Full article

The role of insulin-like growth factor-binding proteins (IGFBPs) in the regulation of carbohydrate metabolism and the development of complications is well established; however, the impact of the glucagon-like peptide-1 receptor agonist semaglutide on IGFBPs has not been previously investigated. We aimed to examine the effects of semaglutide and dipeptidyl peptidase-4 inhibitor sitagliptin therapy on serum levels of IGFBP-1, IGFBP-3, and IGFBP-rp1, and to analyze their associations with anthropometric variables and markers of carbohydrate and lipid metabolism. In this prospective study, we enrolled 34 patients with type 2 diabetes mellitus (T2DM) on metformin monotherapy and 31 age-, sex- and BMI-matched controls. Among the patients, 18 received semaglutide, and 16 were treated with sitagliptin. Anthropometric and laboratory assessments were performed at baseline, 26 and 52 weeks. IGFBP levels were measured using ELISA. Both semaglutide and sitagliptin treatment significantly increased IGFBP-1 levels. IGFBP-3 levels were significantly decreased following sitagliptin therapy. No significant change in IGFBP-rp1 levels was observed with either treatment. Based on multiple regression analysis, the best predictors of IGFBP-1 were insulin and hsCRP, while the best predictor of IGFBP-3 was LDL-C level. Our findings suggest that semaglutide and sitagliptin may exert favorable effects on the GH/IGF-1 axis, potentially contributing to their beneficial metabolic outcomes in patients with T2DM. Full article

Novel antidiabetic drugs introduced in the last decade have not only revolutionized the treatment of type 2 diabetes mellitus but have also changed our cardiovascular risk reduction strategy. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce the risk of atherosclerotic diseases primarily through their complex anti-atherosclerotic effect due to their endothelial function-improving, anti-inflammatory, anti-thrombotic, and plaque-stabilizing effects. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, on the other hand, have a favorable cardiovascular effect, mainly by increasing sodium excretion, reducing plasma volume, enhancing the use of ketone bodies as metabolic substrates in heart and kidney tissues, and reducing oxidative stress and uric acid serum levels. However, when using these two groups of drugs, important questions arise. What criteria should be used to decide on the administration of one or the other class of drugs? Which group of agents can be used more effectively to reduce our patients’ cardiovascular risk? What are the possible adverse effects? What can be gained by combining the two drugs? Our objective was to provide a current literature-based and comparative summary on the mechanisms of action, cardiovascular-risk-reducing efficacy, and safety profiles of these two drug classes, with an emphasis on identifying key factors influencing everyday clinical decision-making. Full article

Background/Objectives: Sodium–glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have shown blood pressure (BP) reduction in type 2 diabetes (T2D). However, head-to-head comparisons in hypertensive patients remain limited. This study assessed the effects of SGLT2i and GLP-1RA on systolic BP (SBP), diastolic BP (DBP), antihypertensive regimen modifications, and adverse events in Saudi patients with both conditions. Methods: A retrospective cohort study was conducted between January 2022 and April 2024 using records from two hospitals. Adults with T2D and hypertension who initiated SGLT2i or GLP-1RA and had ≥2 BP readings were included. BP changes were analyzed with ANOVA; adverse events and treatment discontinuation were assessed with Chi-square and Kaplan–Meier analysis. Results: Of 505 patients, 291 (57.6%) received SGLT2i and 214 received GLP-1RA. Both classes significantly reduced SBP (p < 0.001), and DBP decreased significantly only in the SGLT2i group (p < 0.001). Antihypertensive regimen reduction occurred in 6.9% of patients, most commonly among SGLT2i users (74.3%), while 76.8% remained on the same regimen; the remaining patients had other modifications such as dosage adjustments or changes in individual agents. Adverse events occurred in 6.3% of patients with no group differences. Therapy discontinuation was higher with GLP-1RA (12.6%) versus SGLT2i (2.4%, p < 0.001). Conclusions: Both SGLT2i and GLP-1RA might be considered in patients with T2D and hypertension, with SGLT2i potentially offering additional benefits for DBP reduction and simplifying antihypertensive regimens, which could support clinical decision-making in real-world practice. Full article

Background and Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked with type 2 diabetes mellitus (T2D) and obesity. Despite its growing prevalence, effective pharmacological interventions remain limited, with antidiabetic agents such as glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) showing emerging promise. This study aimed to evaluate the impact of different antidiabetic therapies on hepatic steatosis, fibrosis, and cardiometabolic risk factors in patients with T2D and MASLD from Romania. Materials and Methods: We conducted a prospective observational study involving 256 patients with T2D and MASLD followed up for 6 months. Assessed parameters included anthropometry, glycemic indices, lipid profile, renal function, liver enzymes, and non-invasive evaluation of hepatic steatosis and fibrosis. Patients were 53% women, had a median age of 63 years, a median BMI of 32.2 kg/m², a median baseline CAP of 281 dB/m, a FibroScan of 8.9 kPa, and an HbA1c of 8.0%. Results: CAP decreased significantly from 281 to 245 dB/m, p < 0.0001; FibroScan from 8.9 to 8.0 kPa, p < 0.0001. The largest changes were observed in the GLP-1 RA subgroup (CAP −50 dB/m, FibroScan −1.0 kPa, weight −8.0 kg, HbA1c −0.7%), and in the SGLT2i subgroup (CAP −30.5 dB/m, FibroScan −0.7 kPa, weight −4.0 kg, HbA1c −0.5%). In regression analysis, independent factors associated with CAP improvement included GLP-1 RA therapy (β = 44.5, 95% CI 38.3–50.6, p < 0.0001), SGLT2i therapy (β = 23.4, 95% CI 15.7–31.1, p < 0.0001), and ≥10% weight loss (β = 23.2, 95% CI 12–34.4, p < 0.0001). For FibroScan improvement, GLP-1 RA (β = 1.0, 95% CI 0.8–1.2, p < 0.0001) and SGLT2i (β = 0.5, 95% CI 0.3–0.7, p < 0.0001) therapies were both significant. Conclusions: Antidiabetic therapy, particularly GLP-1 RA, was significantly associated with improvement in hepatic steatosis, fibrosis, and cardiometabolic risk in T2D patients with MASLD beyond the weight reduction effect. However, weight loss and lipid modulation enhance these benefits, supporting the development of integrated therapeutic strategies for this high-risk population. Full article

The aim was to assess the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RA) treatment on the progression of ascending aorta dilatation in patients with type 2 diabetes mellitus (T2DM). A total of 127 T2DM patients with subclinical ascending aortic dilatation (35–45 mm) were prospectively enrolled. Fifty-seven initiated GLP-1 RA therapy (liraglutide, semaglutide, or dulaglutide), while 70 continued on standard care. Ascending aortic diameter was measured by computed tomography angiography (CTA) at baseline and 24 months, alongside circulating markers of vascular remodeling: matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), C-reactive protein (CRP), and osteoprotegerin (OPG). Progression of aortic dilatation was significantly lower in the GLP-1 RA group compared with controls (+0.36 ± 0.20 mm vs. +1.05 ± 0.28 mm; p < 0.001). Therapy correlated with decreased MMP-9 and CRP (p < 0.01) and increased TIMP-1 and OPG (p < 0.05). The use of GLP-1 RA was an independent predictor of low progression, even in multivariate models after adjusting for demographic, metabolic, and biomarker data. GLP-1 RA therapy was associated with reduced progression of ascending aortic dilatation in T2DM, supporting a potential vasoprotective role beyond glucose lowering. Full article

Background: Cardiometabolic syndromes, including diabetes, obesity, and metabolic syndrome, significantly contribute to cardiovascular fibrosis, a major driver of heart failure. Non-coding RNAs (ncRNAs)—notably microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)—have emerged as critical epigenetic regulators of fibrotic remodeling. Recent studies indicate that widely used metabolic modulators can influence ncRNA expression, potentially impacting on cardiovascular fibrosis. This review synthesizes evidence on the interplay between metabolic therapies and ncRNA regulation, with emphasis on therapeutic and biomarker potential of miRNAs. Methods: A literature search was manually curated and conducted on PubMed for studies published mainly in the last decade and evaluating the effects of metformin, sodium-glucose cotransporter-2 (SGLT2) inhibitors, peroxisome proliferator-activated receptor gamma (PPARγ) agonists, glucagon-like peptide 1 (GLP-1) receptor agonists, and fatty acid oxidation inhibitors on ncRNA expression in the context of cardiovascular fibrosis. Data from in vitro, in vivo, and clinical studies were extracted and categorized by drug class, ncRNA target, and functional outcomes. Results: Several metabolic modulators specifically downregulate pro-fibrotic (miR-21, miR-92, H19, and metastasis associated lung adenocarcinoma transcript 1 (MALAT1)) and upregulate anti-fibrotic ncRNAs (miR-29, miR-133a, miR-711, miR-133a, miR-30a and miR-200 family). This results in global attenuation of the transforming growth factor- beta (TGF-β) signaling, which limits extracellular matrix (ECM) accumulation thus improving myocardial compliance. Across drug classes, changes in ncRNA profiles paralleled improvements in fibrosis-related endpoints. Conclusions: Metabolic modulators exert anti-fibrotic effects partly through ncRNA regulation, offering novel therapeutic strategies and potential biomarkers for cardiovascular fibrosis in cardiometabolic disease. Targeting metabolic–ncRNA crosstalk may enable more precise and synergistic interventions for preventing or reversing pathological remodeling. Full article