Search Results (2,009)

Background: Mongolia is experiencing a rapid epidemiologic transition in which high burdens of micronutrient malnutrition, infection, and cardiometabolic disease are simultaneously prevalent. This cross-sectional study sought to understand how nutritional, lifestyle, and cardiometabolic risk factors are distributed among a population at high-risk for tuberculosis (TB), comprising household contacts (HHCs) and healthcare workers, (HCWs) in Ulaanbaatar, Mongolia, and how these factors are associated with TB infection. Methods: A total of 196 HHCs and 241 HCWs were assessed for latent TB infection (LTBI) using the QuantiFERON-TB Gold Plus (QFT-Plus) assay and for diabetes using fingerprick samples for fasting blood glucose. Participants also underwent assessments of their diet and physical activity, nicotine dependence, body mass index, and serum 25(OH)D concentration. We examined associations between assessed risk factors and LTBI using multivariate logistic regression. Results: The prevalence of LTBI was 47% for both HHCs and HCWs. A total of 54% percent of HHCs and 68% of HCWs had low physical activity levels; 63% of HHCs and 95% of HCWs were overweight or obese; 7% of HHCs and 4% of HCWs had impaired or diabetic fasting blood glucose [FBG]; and 49% of HHCs and 70% of HCWs were vitamin D deficient. In a multivariable analysis of HHCs, LTBI was independently associated with lower serum [25(OH)D], and the odds ratio (OR) was 3.18 (95% CI 1.38–7.79; p = 0.009). In contrast, the probability of LTBI did not differ significantly between vitamin D-deficient and non-deficient HCWs, and the OR was 0.89 (95% CI 0.59–1.37; p = 0.42). In a pooled analysis of HHCs and HCWs, the probability of LTBI did not significantly differ between vitamin D-deficient vs. non-deficient participants. The association between serum [25(OH)D] and LTBI among HHCs and HCWs was significantly modified by fasting blood glucose (FBG), such that a lower vitamin D status was significantly more common among those in the highest tertile of FBG than among those in the lowest tertile of FBG. Conclusions: Nutritional, lifestyle, and cardiometabolic risk factors are highly prevalent among HHCs and HCWs with TB in Ulaanbaatar, Mongolia. These findings underscore the importance of simultaneously controlling TB infection, malnutrition, and cardiometabolic risks among HHCs and HCWs to reduce the disease burden in Mongolia. Full article

Background: A major factor in the development of atherosclerosis is the presence of a chronic inflammatory state. The CX₃CL1/CX₃CR1 axis has been implicated in the development of atherosclerosis and cardiovascular disease, but until now, scarce data are available regarding the influence of the CX₃CL1/CX₃CR1 axis in familial combined hyperlipidaemia (FCH). Since FCH is associated with a high risk of cardiovascular disease, the objective of the present study was to assess the presence of alterations in the CX₃CL1/CX₃CR1 axis in patients with FCH and to evaluate the influence of insulin resistance (IR) and sex. Methods: A cohort of 47 subjects with FCH and 38 control subjects was included. We measured the lipid profile, glucose, and insulin levels in plasma, circulating blood CX₃CL1 levels, and CX₃CR1 mRNA expression. Carotid IMT and the presence of atheroma plaques were also evaluated. Results: FCH subjects showed significantly higher activation of the CX₃CL1/CX₃CR1 axis than controls. In addition, FCH individuals with IR showed the worst profile of inflammation status, higher carotid IMT, and a higher prevalence of atherosclerotic plaque compared to controls and FCH patients without IR. However, sex did not influence the CX3CL1/CX3CR1 axis. Conclusions: FCH patients showed an increased CX₃CL1/CX₃CR1 axis, which was positively correlated with IR, but not with sex. These data could partially explain the increased risk of cardiovascular events in primary dyslipidemic patients. Full article

Background/Objectives: Diabetic nephropathy (DN) is a major complication of diabetes and a leading cause of end-stage renal disease, a condition associated with high mortality risks. Recently, supplementation with probiotics and postbiotics has been attracting attention. Especially, metabolites of natural products bioconverted by beneficial bacteria have emerged as a novel therapeutic intervention for metabolic diseases, including diabetes, due to the enhanced bioavailability of their metabolites. This study investigated the alleviating effects of metabolites derived from guava leaf extract bioconverted by Limosilactobacillus fermentum (GBL) on renal inflammation in type 2 diabetic mice. Methods: For this purpose, diabetes was induced in male C57BL/6J mice by a high-fat diet and streptozotocin injection (80 mg/kg BW) twice. Subsequently, mice with fasting blood glucose levels higher than 300 mg/dL were administered metabolites of L. fermentum (LF) (50 mg/kg BW/day) or guava leaf extract bioconverted by L. fermentum (GBL) (50 mg/kg BW/day) by oral gavage for 15 weeks. Results: GBL demonstrated potential in alleviating hyperglycemia-induced DN in diabetic mice. It markedly improved hyperglycemia, glucose tolerance, and morphological alterations, which might stem from activation of key regulators of energy metabolism. GBL uniquely reduced advanced glycation end products (AGEs) and suppressed nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-driven inflammatory pathways, which significantly alleviated oxidative stress and apoptosis. Conclusions: This highlights the distinct therapeutic efficacy of GBL in addressing DN, primarily through its effects on renal inflammation. Taken together, GBL can be used as a promising nutraceutical to mitigate hyperglycemia and its associated renal inflammation, thereby alleviating the progression of DN. Full article

Objective: This study aimed to evaluate the association between the triglyceride–glucose index (TGI) and the risk of cardiovascular disease in patients with type 2 diabetes mellitus. Methods: This study included 1348 type 2 diabetic patients who attended the endocrinology clinic at Jordan University Hospital between March 2023 and September 2023. Medical records were reviewed to identify patients with documented cardiovascular disease, and the triglyceride–glucose index (TGI) was calculated for each patient. Results: Our results showed that the TGI was higher among patients who developed any major adverse cardiovascular event (MACE), coronary artery disease (CAD), congestive heart failure (CHF), and/or myocardial infarction (MI) compared to those who did not (p < 0.001 for all comparisons). Significantly higher TGI values in males were associated with higher odds of a MACE, stroke, and CHF; higher TGI values in females were associated with higher odds of a MACE, CAD, and MI. Higher TGI values in patients younger than 60 were associated with higher odds of a MACE, CAD, CHF, and MI, while in patients older than 60, higher TGI values were associated with higher odds of CAD and MI. The TGI value that was the most predictive of a MACE in our population was >9.36, >9.39 for CAD, and >9.40 and >9.39 for CHF and MI, respectively. Conclusion: The TGI was shown to be associated with a significantly higher risk of a MACE, CAD, CHF, and MI in the whole population, along with stroke in males only. The TGI was more strongly associated with MACEs in patients younger than 60 years compared to older patients. In conclusion, the TGI was associated with cardiovascular outcomes in this diabetic cohort; however, its discriminative ability was modest (AUC 0.55–0.64). This indicates that the TGI alone is insufficient as a predictive tool and should be interpreted alongside established risk factors. Prospective studies are needed to clarify its incremental value in risk prediction. Full article

Atrial fibrillation (AF) is the most common arrhythmia worldwide, a major cause of heart failure and stroke, and carries a significant healthcare burden. Atrial cardiomyopathy (ACM) provides the structural and electrophysiological basis for AF, while metabolic dysregulation, particularly insulin resistance (IR), is increasingly recognized as a key factor exacerbating atrial remodeling. However, due to the complexity and high cost of IR measurement procedures, no reliable, user-friendly, and practical tool supporting AF risk stratification has yet been identified in clinical practice. To address this gap, we conducted a literature search in various databases and found an increasing body of research indicating that the triglyceride–glucose index (TyG index) is a simpler, more cost-effective alternative for identifying adverse metabolic profiles and the AF risk. This narrative review describes the existing literature and explores the potential mechanisms underlying changes in the TyG index and its clinical applications, while also discussing the challenges facing the use of this index and future research directions. In summary, the current evidence suggests that the TyG index is a promising but not yet established risk assessment biomarker for AF. Full article

Obesity is a chronic, multifactorial disease characterized by excess body fat and is a major risk factor for various metabolic disorders. Bioactive compounds from the diet have been recognized for their role in preventing chronic non-communicable diseases and as adjuvants in managing endocrine–metabolic dysfunctions. Hibiscus sabdariffa L. (HSL) is rich in bioactive compounds with antioxidant, antihypertensive, and antihyperlipidemic properties. This study evaluated the effects of HSL flower extract supplementation on body composition, lipid profile, and biochemical parameters in both eutrophic and high-fat diet-induced obese rats. Thirty-two Wistar rats were assigned to four groups: control, control plus HSL extract, high-fat diet, and high-fat diet plus HSL extract. The extract was administered orally at 150 mg kg⁻¹ for thirty days. Dual-energy X-ray absorptiometry revealed that HSL supplementation significantly attenuated fat mass gain (from 98 g to 75 g) and adiposity indices (10.23 to 8.86) in obese rats without altering total body mass. Moreover, the HSL extract improved lipid profiles by reducing LDL cholesterol from 23 to 13 mg dL⁻¹ and exhibited potential hepatoprotective effects linked with decreased ALT (40 to 26.7 U L⁻¹) and total bilirubin (0.12 to 0.07 mg dL⁻¹) levels. Although glucose metabolism parameters had no significant differences, a trend toward improved insulin sensitivity was observed. These results suggest that the aqueous HSL extract may exert cardioprotective, hepatoprotective, and anti-obesity effects, supporting its potential as a complementary therapeutic agent in obesity and related metabolic disorders. Full article

Background: Uraemic cardiomyopathy (UCM), the cardiac manifestation of chronic kidney disease, represents a significant clinical challenge that is often underdiagnosed despite being one of the strongest predictors of mortality in the chronic kidney disease (CKD) population. It develops through pathophysiological mechanisms unique to the uraemic state—left ventricular hypertrophy, myocardial fibrosis, and diastolic dysfunction—that often progress silently, sometimes even without traditional cardiovascular risk factors. Purpose: This review synthesises nephrology-centric mechanisms with clinical phenotypes and contemporary imaging (including CMR T1/T2 mapping and ECV), and proposes a CKD-stage–tailored diagnostic–therapeutic framework. It offers a distinct perspective by integrating the complex pathophysiology of UCM with practical diagnostic approaches and evolving management strategies, differentiating it from prior cardiology-focused overviews. Methods: A comprehensive literature search was conducted across Ovid MEDLINE, Embase, PubMed, Google Scholar, BMJ Best Practice, and UpToDate for studies published up to March 2025. Key findings were extracted from the final evidence set and manually verified for relevance. This review introduces a patho-mechanical cascade model of uraemic cardiomyopathy, integrating toxin-driven, metabolic, and haemodynamic axes. Nephrology-led screening protocols are proposed, leveraging proteomics and strain echo, and advocate mineralocorticoid receptor antagonists with sodium–glucose co-transporter-2 (SGLT2) inhibitor initiation at CKD Stage 3a. Cardiorenal clinics are essential for improved outcomes. Key Insights: UCM develops from a multifactorial process. This involves neurohormonal activation, oxidative stress, chronic inflammation, and exposure to toxins such as indoxyl sulfate and p-cresyl sulfate, arising from uraemia. Diagnosis is challenging, masked by overlapping features of fluid overload and anaemia. SGLT2 inhibitors, non-steroidal mineralocorticoid antagonists, and renin–angiotensin–aldosterone system modulation offer promising interventions. The effect of the dialysis modality, its timing, and renal transplantation on cardiac remodelling also emerging from recent studies. Conclusions: UCM sits at the intersection of two failing organ systems. Managing it effectively requires a paradigm shift to incorporate pharmacological and early diagnostic interventions and the integration of cardiology and nephrology care, and the timely implementation of interventions. Full article

Background/Objectives: As the global population ages, cardiovascular disease (CVD) emerges as a critical challenge for public health, with chronic inflammation identified as a key contributing risk factor. As a modifiable lifestyle factor, diet plays a critical role in the prevention of CVD. Given the established link between diet and inflammation, clarifying the relationship between dietary inflammatory potential and cardiovascular health (CVH) is of significant public health importance. This study aimed to evaluate the association between dietary inflammatory potential and CVH in an elderly population, and to explore the related role of the gut microbiota. Methods: Dietary inflammatory potential was quantified using the Dietary Inflammatory Index (DII), CVH was assessed by the American Heart Association’s Life’s Essential 8 (LE8) score, and gut microbiome analysis was profiled by 16S rRNA gene sequencing. Results: Results showed that higher DII scores, indicative of a pro-inflammatory dietary pattern, were significantly linked to reduced LE8 scores, suggesting an inverse association between dietary inflammatory potential and CVH. Based on the gut microbiome, participants with high CVH exhibited greater α diversity compared with those with low CVH, while both α and β diversity were higher in the anti-inflammatory diet group than in the pro-inflammatory diet group. These results indicate that anti-inflammatory diets may be associated with better CVH, possibly through the preservation of the ecological balance of the gut microbiota. Correlation analyses further pointed to several genera potentially associated with both dietary inflammatory potential and CVH. Functional predictions suggested that variation in dietary inflammatory potential could be linked to differences in microbial metabolic functions relevant to energy, lipid and glucose metabolism, and inflammatory processes. Conclusions: In conclusion, this study provides novel evidence linking dietary inflammatory potential, gut microbiota, and CVH in older adults, and offers preliminary insights for dietary interventions and microbiota-targeted strategies in CVD prevention. Full article

Background: Rheumatoid arthritis and periodontitis are chronic inflammatory diseases linked to systemic complications, including increased cardiovascular risk. The impact of glycemia, lipid profile and atherogenic cardiovascular risk indices in patients with rheumatoid arthritis (RA) and periodontitis, compared to controls, has not yet been evaluated. We aimed to analyze whether periodontitis acts as an aggravating factor in this relationship. Methods: In a case–control study, we assessed biochemical, RA-related markers and four atherogenic indices (Atherogenic Index of Plasma, Castelli Risk Index I, Castelli Risk Index II, and Triglyceride–Glucose Index). Periodontitis was evaluated using a gingival inflammation index (BOP) and a periodontal severity index (PIRIM). Multiple linear regression models were used to analyze whether periodontitis had a differential effect in RA cases versus controls. Results: A total of 46 participants were included (32 RA cases, 14 controls). Periodontitis was more prevalent among cases (62.5% vs. 28.5%). BOP was significantly higher in RA patients (p < 0.001) and associated with LDLC (p = 0.031). Both BOP and PIRIM correlated with higher CRI-1 and CRI-2 values across groups. PIRIM was also linked to increased LDLC (p = 0.018) and decreased HDLC (p = 0.003). Conclusions: RA and periodontitis appear to interact synergistically and are associated with a more atherogenic profile. These findings highlight periodontal health as a potentially modifiable factor in reducing cardiovascular risk in RA patients. Full article

Background: Childhood obesity and cardiometabolic disturbances are growing global health concerns. This study aimed to assess the prevalence of excess body weight, body fat, and selected cardiometabolic risk factors in school-aged children and adolescents, focusing on sex- and age-related differences. Methods: A cross-sectional study was conducted among 318 Polish participants aged 6–17 years, including 169 children (6–12 years) and 149 adolescents (13–17 years). Anthropometric, blood pressure (BP), and fasting blood lipid and glucose measurements were collected and analyzed by age group (children 6–12 years; adolescents 13–17 years) and sex. Results: The prevalence of overweight and obesity was 18.5% (BMI-based) and 26.1% (body fat-based). Abdominal obesity and stage I–II hypertension were observed in 24.5% and 23.6% of participants, respectively. Children had higher rates of excess body fat, abdominal obesity, elevated BP, and lipid abnormalities than adolescents. Among adolescents, girls more frequently presented with borderline/high total cholesterol and Low-Density Lipoprotein (LDL cholesterol) and borderline/low High-Density Lipoprotein (HDL cholesterol), while boys more often had elevated BP. In girls, elevated triglycerides (TGs) were independently associated with abdominal obesity (odds ratio (OR) = 2.36, p = 0.015) and hypertension (OR = 2.47, p = 0.023); no such associations were observed in boys. Conclusions: Cardiometabolic risk factors may appear early in life and differ by age and sex. Routine screening and early interventions, particularly targeting lipid abnormalities in girls, are essential to prevent long-term health consequences. Full article

Background/Objectives: Hepatic steatosis, a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD), is closely associated with systemic metabolic dysfunction. However, the cumulative impact of metabolic risk factors on liver fat content remains underexplored. To evaluate the association between metabolic risk factors and hepatic steatosis severity using magnetic resonance imaging proton density fat fraction (MR-PDFF) measurement, and to assess the cumulative effect of multiple metabolic abnormalities. Methods: In this cross-sectional study, MASLD patients (n = 132, aged ≥ 18 years, age: 61.3 ± 10.3, male: 54, female: 78) underwent metabolic risk assessment and MR-PDFF liver fat content measurement. The association between certain metabolic risk scores (obesity/overweight, hypertension, hypercholesterolemia, hypertriglyceridemia, impaired fasting glucose or type 2 diabetes mellitus) both continuous and categorized, as well as liver fat content was analyzed using linear regression models. The cumulative effect of increasing metabolic risk was further explored with subgroup comparisons. Results: A significant positive association was observed between continuous metabolic risk scores and MR-PDFF values (β = 0.021, p < 0.001). Participants with higher cumulative metabolic risk (4 and 5 risk factors group) showed significantly higher liver fat content compared to the reference group (p < 0.01) (MetfO0 = 5.7 ± 5.9%; MetfO1 = 11.6 ± 9.5%; MetfO2 = 7.9 ± 5.6%; MetfO3 = 10.2 ± 7.9%; MetfO4 = 16.4 ± 11.0%; MetfO5 = 17.8 ± 9.5%). Intermediate metabolic risk categories showed a trend toward increased steatosis but did not reach statistical significance. Conclusions: Cumulative metabolic risk is strongly associated with increased hepatic fat accumulation. These findings underscore the need for early identification and management of metabolic risk factors to prevent the development and progression of hepatic steatosis. Full article

Background/Objectives: HIV infection has been associated with an increased incidence of non-communicable comorbidities, including metabolic disorders. This phenomenon has been linked to gut microbiota dysbiosis, which involves not only changes in bacterial composition but also functional alterations in metabolite production. The objective of this study was to describe the impact of intestinal microbial metabolomics on the development of type 2 diabetes in people living with HIV. Methods: This study provides a narrative synthesis of current evidence addressing the role of gut microbiota-derived metabolites in immunometabolic regulation and their implications in HIV-associated type 2 diabetes. Results: Microbial metabolites play a fundamental role in regulating key physiological processes such as intestinal permeability, systemic immune activation, and glucose metabolism. Compounds such as short-chain fatty acids, tryptophan catabolites, secondary bile acids, trimethylamine N-oxide, and imidazole propionate have been shown to significantly influence immunometabolic balance. In people living with HIV, these microbial products may exert diverse effects depending on their chemical nature and the molecular pathways they activate in peripheral tissues. The interaction between dysbiosis, chronic low-grade inflammation, and HIV-associated metabolic disturbances may contribute to the early onset of type 2 diabetes beyond traditional risk factors. Conclusions: Recognizing the role of microbial metabolites in the context of HIV infection is essential to broaden our pathophysiological understanding of associated metabolic comorbidities. It also opens opportunities to develop more comprehensive diagnostic and therapeutic strategies that include modulation of the gut microbiota and its metabolic activity for the prevention and management of type 2 diabetes in this population. Full article

Background: This multicenter cross-sectional study aimed to assess the prevalence of vascular, hepatic, cardiac, endocrine, and bone complications and to identify factors associated with their occurrence in adult patients with neo-transfusion-dependent thalassemia (neo-TDT). Methods: A total of 140 adult neo-TDT patients (defined as receiving >4 transfusions/year; mean age 44.3 ± 12.1 years; 56.4% female) were retrospectively enrolled from the Extension–Myocardial Iron Overload in Thalassemia (E-MIOT) network. Iron overload (IO) was assessed by magnetic resonance imaging and complications were classified according to established clinical criteria. Logistic regression analyses were performed to investigate associations of complications with age, sex, splenectomy status, chelation therapy, hemoglobin < 9 g/dL, ferritin ≥ 1000 ng/mL, and hepatic, pancreatic, and cardiac IO. Results: Complications affecting fewer than 5% of patients—including leg ulcers, cirrhosis, thrombosis, heart failure, and hypoparathyroidism—were excluded from statistical analysis. Bone metabolism disorders were the most prevalent complications (68.6%), followed by impaired glucose metabolism (15.7%). The prevalence of other complications was: extramedullary hematopoiesis (EMH) 19.3%, pulmonary hypertension (PH) 7.1%, arrhythmias 12.1%, hypogonadism 11.4%, and hypothyroidism 15.0%. Male sex was independently associated with EMH (odds-ratio [OR] = 2.67; p = 0.027). Hepatic IO was the only significant predictor of PH (OR = 4.12; p = 0.047). Arrhythmias were strongly associated with older age (OR = 22.67; p < 0.0001), while both older age (OR = 4.42; p = 0.004) and pancreatic IO (OR = 7.40; p = 0.012) were independently associated with impaired glucose metabolism. No significant associations were identified for hypogonadism, hypothyroidism, or bone metabolism disorders. Conclusion: This study offers updated insights into the burden of complications in neo-TDT patients and highlights specific risk factors that may inform comprehensive, multidisciplinary surveillance strategies. Full article

Objectives: This study aimed to determine the incidence of postoperative deep vein thrombosis (DVT) and pulmonary embolism (PE) following orthopedic surgeries and to identify independent clinical, laboratory, and procedural factors associated with thromboembolic risk. Materials and Methods: A retrospective cohort analysis was conducted on 300 patients who underwent elective or emergency orthopedic surgeries (hip/knee arthroplasty, fracture fixation, and spinal procedures) between January 2020 and December 2024 at two tertiary centers. Demographic, clinical, and biochemical data were collected. Patients were stratified into two groups: those who developed DVT/PE and those who did not. Univariate analyses were performed to identify significant factors, and a multivariate logistic regression model with stepwise variable selection was applied in accordance with the events-per-variable (EPV) criterion. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the discriminative performance of significant predictors. Results: Among 300 patients who underwent orthopedic surgery, postoperative deep vein thrombosis (DVT) and/or pulmonary embolism (PE) occurred in 50 cases (16.7%). Patients who developed thromboembolic events were older (72.5 ± 8.7 vs. 65.2 ± 10.1 years, p < 0.001), had higher body mass index (32.1 ± 5.3 vs. 28.3 ± 4.5 kg/m², p < 0.001), and showed a greater prevalence of diabetes mellitus (40% vs. 20%, p < 0.01) and chronic kidney disease (24% vs. 10%, p < 0.001) compared to those without DVT/PE. Laboratory analyses revealed significantly elevated neutrophil count, D-dimer, C-reactive protein (CRP), glucose, and troponin levels in the DVT/PE group. In the stepwise multivariate logistic regression model, age (OR = 1.44, p = 0.003), diabetes mellitus (OR = 2.88, p = 0.046), chronic kidney disease (OR = 2.33, p = 0.014), D-dimer (OR = 2.15, p = 0.019), and immobilization duration (OR = 2.21, p = 0.028) emerged as independent predictors of thromboembolic events. ROC analysis revealed that D-dimer > 0.9 mg/L had the highest discriminative performance (AUC = 0.89, sensitivity 88%, specificity 84%, p = 0.003), followed by troponin > 0.5 U/L (AUC = 0.86, p = 0.005), immobilization > 3 days (AUC = 0.82, p = 0.012), and age > 65 years (AUC = 0.74, p = 0.021). Conclusions: DVT and PE remain significant postoperative complications with a multifactorial etiology in orthopedic surgeries. Advanced age, comorbidities (such as diabetes mellitus and chronic kidney disease), and elevated inflammatory and metabolic markers (including neutrophil count, glucose, CRP, and D-dimer), together with procedural factors like prolonged immobilization, were identified as independent risk factors. Early recognition of these high-risk features and implementation of individualized prophylaxis strategies may improve postoperative outcomes and reduce thromboembolic risk. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses several cardiometabolic risk factors (obesity, insulin resistance, diabetes, and dyslipidemia), in addition to hepatic steatosis. Therefore, treatment is often challenging and frequently involves polypharmacy. This study investigated whether the combination of empagliflozin/metformin improves MASLD disease outcomes in an experimental model of metabolic syndrome (MS). To evaluate the efficacy of the empagliflozin/metformin (12.5/850 mg/kg/day/30 days) combination, male Wistar rats (200–220 g) were fed a Western-type diet and sugary drink to induce MS. Biochemical parameters, markers of liver damage, oxidative stress, and histopathological analysis were assessed. Also, the expression of transcription factors associated with carbohydrate and lipid metabolism and the modulation of oxidative stress were assessed. The analyses were performed with the combination and with the drugs independently. The combination empagliflozin/metformin decreased body weight, plasma triglycerides, and total cholesterol levels, while improving fasting blood glucose, oral glucose tolerance test, and plasma HDL-cholesterol levels. Additionally, it prevented hepatic hypertrophy, liver damage at both biochemical and histological levels, and intrahepatic lipid accumulation. The combination also demonstrated a significantly greater effect in improving mitochondrial function and reducing oxidative stress by modulating the Nrf2-mediated pathway. The empagliflozin/metformin combination therapy mitigates MASLD progression, likely by improving liver and mitochondrial function, and attenuating oxidative stress. Notably, co-therapy shows greater beneficial effects than single treatments. This protective effect appears to involve modulation of key transcription factors regulating lipid and carbohydrate metabolism, as well as influencing endogenous antioxidant defenses. Full article