Metabolic dysfunction-associated steatotic liver disease: heterogeneous pathomechanisms and effectiveness of metabolism-based treatment

The Lancet Diabetes & Endocrinology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 1, 2024

Язык: Английский

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Glucagon‐Like Peptide‐1 Receptor Agonists and Liver Outcomes in Patients With MASLD and Type 2 Diabetes

Alimentary Pharmacology & Therapeutics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

ABSTRACT Background and Aims Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) have demonstrated long‐term liver benefits in patients with metabolic dysfunction‐associated steatotic disease (MASLD) type 2 diabetes (T2D). However, no direct comparison between these therapies has been conducted. This study aimed to compare major adverse outcomes (MALOs) GLP‐1 RAs SGLT2is MASLD T2D. Methods Using the TriNetX Research Network, a multinational multi‐institutional database, we identified adults T2D who received their first prescription for either RA or an SGLT2i January 2010 June 2023. We conducted propensity score‐matched (PSM) cohort comparing new users of SGLT2is. The primary outcome was risk MALOs, composite endpoint consisting decompensated cirrhosis events, hepatocellular carcinoma, transplantation. Secondary included all‐cause mortality individual components outcome. Results 15,176 pairs treated SGLT2i. adjusted hazard ratio (HR) MALO associated relative 0.84 (95% confidence interval [CI]: 0.73–0.97; incidence rate: 88.9 versus 105.3 events per 10,000 person‐years), primarily driven by reduction (adjusted HR: 0.83, 95% CI: 0.71–0.96). were lower 0.84, 0.75–0.94). Conclusion are better compared

Язык: Английский

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Glucagon like peptide-1 receptor agonists as a promising therapeutic option of metabolic dysfunction associated steatotic liver disease and obesity: hitting two targets with one shot

Current Opinion in Gastroenterology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Purpose of review Obesity and type 2 diabetes mellitus (T2DM) are significant global health challenges, closely linked to metabolic dysfunction-associated steatotic liver disease (MASLD). Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promise in treating T2DM obesity, but their potential for managing MASLD is still being explored. This aims examine the current progress using GLP-1RAs treatment evaluate emerging dual triple hormonal as future therapeutic options. Recent findings been effective controlling blood sugar levels, promoting weight loss, improving cardiovascular kidney function. Furthermore, they benefits function patients with MASLD. GLP-1, a key incretin hormone, influences glucose metabolism, appetite, insulin sensitivity while affecting gastric emptying potentially reducing fat deposition liver. developments include various formulations different administration dosing options, expanding use. Summary become central management T2DM, possibly due ability lower HbA1c, aid reduction, provide protection. As research continues, next evolution incretin-based therapies, offering promising new strategies addressing future.

Язык: Английский

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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, Год журнала: 2025, Номер unknown

Опубликована: Фев. 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.

Язык: Английский

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From adiposity to steatosis: metabolic dysfunction-associated steatotic liver disease, a hepatic expression of metabolic syndrome – current insights and future directions

Clinical Diabetes and Endocrinology, Год журнала: 2024, Номер 10(1)

Опубликована: Дек. 2, 2024

Язык: Английский

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MAFLD Pandemic: Updates in Pharmacotherapeutic Approach Development

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(7), С. 6300 - 6314

Опубликована: Июнь 21, 2024

With around one billion of the world's population affected, era metabolic-associated fatty liver disease (MAFLD) pandemic has entered global stage. MAFLD is a chronic progressive with accompanying metabolic disorders such as type 2 diabetes mellitus and obesity which can progress asymptomatically to cirrhosis subsequently hepatocellular carcinoma (HCC), for date there are almost no approved pharmacologic options. Because very complex etiology it also affects extrahepatic organs, multidisciplinary approach required when comes finding an effective safe active substance treatment. The optimal drug should diminish steatosis, fibrosis inflammation in liver, winner authorisation seems be that significantly improves histology. Saroglitazar (Lipaglyn

Язык: Английский

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Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease: A cross-sectional study

World Journal of Gastroenterology, Год журнала: 2025, Номер 31(7)

Опубликована: Янв. 18, 2025

Skeletal muscle alterations (SMAs) are being increasingly recognized in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and appear to be associated deleterious outcomes these patients. However, their actual prevalence pathophysiology remain elucidated. To determine the of SMAs assess significance circulating myokines as biomarkers MASLD. strength mass were measured a cross-sectional study cohort 62 fulfilling MASLD criteria, recruited from outpatient clinics tertiary level hospital. The degree fibrosis steatosis was studied using abdominal ultrasound transitional elastography. Anthropometric characteristics well serum levels different also determined cohort. Statistical analysis performed comparing results according steatosis. No significant differences found both skeletal between stages fibrosis. Interestingly, fibroblast growth factor-21 (FGF21) significantly higher advanced hepatic (F3-F4) than those lower (F0-F2) (197.49 ± 198.27 pg/mL vs 95.62 83.67 pg/mL; P = 0.049). In addition, severe hepatosteatosis (S3) exhibited irisin (1116.87 1161.86 pg/mL) grades (S1-S2) (385.21 375.98 0.001). uncommon studied. Higher FGF21 detected fibrosis, respectively, potential implications biomarkers.

Язык: Английский

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An insight on the additive impact of type 2 diabetes mellitus and nonalcoholic fatty liver disease on cardiovascular consequences

Molecular Biology Reports, Год журнала: 2025, Номер 52(1)

Опубликована: Янв. 28, 2025

Язык: Английский

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Da NAFLD a MASLD: pillole per endocrinologi

L Endocrinologo, Год журнала: 2025, Номер unknown

Опубликована: Фев. 10, 2025

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Liver specific transgenic expression of CYP7B1 attenuates early Western diet-induced MASLD progression

Journal of Lipid Research, Год журнала: 2025, Номер unknown, С. 100757 - 100757

Опубликована: Фев. 1, 2025

Effect of liver specific oxysterol 7α-hydroxylase (CYP7B1) overexpression on the Western diet (WD)-induced metabolic dysfunction-associated steatotic disease (MASLD) progression was studied in mice. Among various hepatic genes impacted during MASLD development, CYP7B1 is consistently suppressed multiple mouse models and human cohorts. enzyme suppression leads to accumulations bioactive oxysterols such as (25R)26-Hydroxycholesterol (26HC) 25-hydroxycholesterol (25HC). We challenged transgenic (CYP7B1hep.tg) overexpressing mice with ad libitum WD feeding. Unlike their wild type (WT) counterparts, WD-fed CYP7B1hep.tg developed no significant hepatotoxicity evidenced by histology, lipid quantifications, serum biomarker analyses. Hepatic 26HC 25HC levels were maintained at basal levels. The comparative gene expression/lipidomic analyses between WT revealed that chronically accumulated initiates LXR/PPAR-mediated fatty acid uptake lipogenesis which surpasses metabolism export; compromising functions. In addition, major pathways related oxidative stress, inflammation immune system including retinol metabolism, arachidonic linoleic significantly All unaltered liver. Furthermore, nucleus but not response WD. This data strongly suggested these two are specifically important nuclear transcriptional regulation for described cytotoxic pathways. conclusion, this study represents a "proof-of-concept" maintaining normal mitochondrial cholesterol expression prevents oxysterol-driven toxicity; thus attenuating progression.

Язык: Английский

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