Pharmacological treatment options for metabolic dysfunction‐associated steatotic liver disease in patients with type 2 diabetes mellitus: A systematic review

European Journal of Clinical Investigation, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 12, 2025

Abstract Background Metabolic dysfunction‐associated steatotic liver disease (MASLD) is closely related to type 2 diabetes mellitus (T2DM) through a common root in insulin resistance. The more severe stage, metabolic steatohepatitis (MASH), increases the risk for cardiovascular complications, cirrhosis and hepatocellular carcinoma. Several trials investigating established antidiabetic‐drugs patients with T2DM MASLD have yielded promising results. Therefore, we aimed systematically review effect of T2DM‐drug treatment on MALSD parameters. Methods Medical databases were searched until January 2025 controlled MASLD/MASH. Studies that evaluated T2DM‐medication severity MASLD/MASH included. quality studies was assessed by three independent reviewers using set Cochrane risk‐of‐bias tools. Results Of 1748 references, 117 fulfilled inclusion‐criteria eligibility full‐text. Fifty‐two articles Data included total 64.708 study populations ranged from 9 50.742. Heterogeneity study‐design analysis hampered comparability Most evidence present GLP‐1 receptor agonists, SGLT2‐inhibitors PPAR‐γ‐agonists regression fibrosis MASH. Conclusion value improvement vary significantly design, size quality. PPAR‐γ‐agonists, may all be preferred pharmacological interventions T2DM. Newer agents like dual GLP‐1/GIP or triple GLP‐1/GIP/Glucagon agonists will likely play an important role near future.

Language: Английский

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Gut Microbiota and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Emerging Pathogenic Mechanisms and Therapeutic Implications

Livers, Journal Year: 2025, Volume and Issue: 5(1), P. 11 - 11

Published: March 4, 2025

Non-alcoholic fatty liver disease (NAFLD), recently redefined as metabolic dysfunction-associated steatotic (MASLD), is the most common cause of chronic worldwide. Characterized by excessive hepatic fat accumulation, this encompasses a spectrum from simple steatosis to more severe forms, including steatohepatitis, fibrosis, and cirrhosis. Emerging evidence highlights pivotal role gut dysbiosis in pathogenesis MASLD. Dysbiosis disrupts gut–liver axis, an intricate communication network that regulates metabolic, immune, barrier functions. Alterations microbiota composition, increased permeability, translocation pro-inflammatory metabolites/factors have been shown trigger inflammatory fibrotic cascades, exacerbating inflammation injury. Recent studies identified microbiome signatures associated with MASLD, offering promise non-invasive diagnostic biomarkers paving way for new potential therapeutic strategies targeting dysbiosis. This review explores crucial MASLD need further targeted research field validate microbial optimize strategies. Comprehensive understanding axis may enable innovative approaches, transforming clinical management

Language: Английский

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Mannose reduces fructose metabolism and reverses MASH in human liver slices and murine models in vivo

Hepatology Communications, Journal Year: 2025, Volume and Issue: 9(4)

Published: March 21, 2025

Background: Fibrosis drives liver-related mortality in metabolic dysfunction–associated steatohepatitis (MASH), yet we have limited medical therapies to target MASH-fibrosis progression. Here report that mannose, a simple sugar, attenuates MASH steatosis and fibrosis 2 robust murine models human liver slices. Methods: The well-validated fat-and-tumor model for was employed. Mannose supplied the drinking water at start (“Prevention” group) or week 6 of 12-week regimen (“Therapy” group). vivo antifibrotic effects mannose supplementation were tested second carbon tetrachloride (CCl 4 )-induced fibrosis. A quantitative automated digital pathology approach used comprehensively assess phenotypes. also vitro primary mouse hepatocytes conditioned with free fatty acids alone fructose, precision-cut slices from patients end-stage cirrhosis. Results: Oral improved both CCl models, as well slice samples. reduced mice, . Ketohexokinase, main enzyme fructolysis, decreased whole liver, cultured hepatocytes, Removal fructose overexpression ketohexokinase each abrogated antisteatotic mannose. Conclusions: This study identifies novel therapeutic candidate mitigates by dampening hepatocyte expression exerts independent tissue

Language: Английский

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Advancing precision medicine in metabolic dysfunction-associated steatotic liver disease

Trends in Endocrinology and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

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Comparative efficacy and safety of pharmacologic therapies for metabolic dysfunction‐associated steatotic liver disease over 24 weeks in reducing liver steatosis and fibrosis: A network meta‐analysis

Diabetes Obesity and Metabolism, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Abstract Aims Metabolic‐associated steatotic liver disease (MASLD) is a prevalent chronic condition associated with significant morbidity and mortality. Effective pharmacological interventions targeting steatosis fibrosis are essential to improving patient outcomes. This study aims systematically compare the efficacy safety of various pharmacologic therapies for MASLD over 24 weeks using comprehensive network meta‐analysis. Materials Methods A systematic review meta‐analysis were conducted on randomized controlled trials (RCTs) evaluating treatments MASLD. The primary outcomes changes in (measured by magnetic resonance imaging proton density fat fraction) elastography‐derived stiffness measurement), assessed through adverse events. Bayesian framework was employed integrate data across treatments, generating rankings safety. Results search databases, identifying 23 RCTs from 10 144 initial records. For reduction, resmetirom showed most improvement (mean difference: −3.86, 95% confidence interval [CI]: −7.33 −0.39) compared placebo. In terms improvement, pegozafermin demonstrated greatest effect (−4.85, CI: −5.50 −4.19). Most acceptable profiles, efruxifermin showing slightly higher events (0.32, 0.06–0.70) Conclusions demonstrates varying MASLD, emerging as particularly promising fibrosis, respectively. While exhibited favourable careful monitoring warranted, due its elevated event profile. These findings provide valuable evidence guide clinical decision‐making management, though longer‐term studies needed confirm durability these therapeutic effects further establish profiles.

Language: Английский

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Sea buckthorn triterpenic acids alleviates metabolic dysfunction-associated steatotic liver disease via modulation of liver biochemistry, lipid metabolism and AMPK/Nrf2/NF-κB signaling pathway

Food Bioscience, Journal Year: 2025, Volume and Issue: unknown, P. 106611 - 106611

Published: April 1, 2025

Language: Английский

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Cell-specific regulation of insulin action and hepatic fibrosis by CEACAM1

Metabolism and Target Organ Damage, Journal Year: 2024, Volume and Issue: 4(4)

Published: Sept. 26, 2024

The incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) has reached an epidemic rise worldwide. is a constellation broad range and histopathologic abnormalities. It begins with hepatic steatosis progresses to steatohepatitis (MASH), including fibrosis, apoptosis, cell injury. Despite ample research effort, the pathogenesis not been fully delineated. Whereas insulin resistance implicated in early stages disease, its role fibrosis remains controversial. We have focused our studies on carcinoembryonic antigen-related adhesion molecule 1 (CEACAM1) hepatocytes endothelial cells histopathological dysregulation MASH. Patients MASH exhibit lower CEACAM1 progressive decline as stage advances. In mice, conditional deletion impairs clearance cause hyperinsulinemia-driven even when mice are fed regular chow diet. contrast, causes inflammation-driven without adversely affecting metabolism (mice remain insulin-sensitive do develop steatosis). Thus, this review provides vivo evidence that supports or discards injury fibrosis.

Language: Английский

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Dawn of an era of effective treatments for MAFLD

Portal hypertension & cirrhosis, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 24, 2024

Abstract Fatty liver disease is a commonly occurring resulting in hepatic and extrahepatic complications. To date, there have been few available treatments beyond conventional lifestyle modification. While modifications weight loss >10% shown to be beneficial for metabolic dysfunction‐associated steatohepatitis (MASH), the majority of patients, this difficult achieve. The recent approval resmetirom (a thyroid hormone receptor beta agonist) by Food Drug Administration following positive results histological outcomes phase 3 trial has opened door new (dysfunction)‐associated fatty (MAFLD) MASH. There are currently number trials targeting variety signaling pathways involved pathogenesis that also promising. This review focuses on MAFLD MASH, ongoing clinical trials, unresolved controversies area.

Language: Английский

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