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

Alimentary Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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

Language: Английский

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GLP-1 receptor agonists in diabetes and weight loss: the double-edged sword of innovation and risks

Frontiers in Clinical Diabetes and Healthcare, Journal Year: 2025, Volume and Issue: 5

Published: Jan. 9, 2025

In recent years, glucagon-like peptide-1 (GLP-1) receptor agonists have gained widespread popularity not only as effective agents in the management of type 2 diabetes but also for their beneficial impact on weight loss. Additionally, this surge interest has been underpinned by pleiotropic effects and spurred further investigation into potential applications beyond care. However, expanding adoption GLP-1 brings with it a set challenges complications. With promising therapeutic comes an increased scrutiny side effects.GLP-1 mimic action native peptide, enhancing insulin secretion, suppressing glucagon release, slowing gastric emptying, increasing satiety. Initially introduced to treat diabetes, they were found important effect loss; paradigm shift medical obesity may -in fact -be imminent, per opinion non-medical pundits [1][2][3]. Drugs like semaglutide, liraglutide or tirzepatide (a dual GIP analog) led significant reduction participants clinical trials real-world settings, making them popular patients physicians alike.The success lies multifaceted mechanisms, which address complex physiological pathways hunger, satiety, glucose metabolism. These drugs target pancreas gut brain's hypothalamic appetite-regulating centers. Some analogs be attributed actions central nervous system neurotransmitter secretion/action; enhance gamma-aminobutyric acid (GABA) activity, restore dopaminergic activity act parallel peptide YY (PYY) [4][5][6]. sense, are redefining approach metabolic disease addressing glycemic control influencing body cardiovascular health. Currently, long-term consequences analog use over 1.5 -2 years look promising; published meta-analyses, reduced morbidity mortality noted, whereas no appearance gastrointestinal neoplasia observed [7][8].The foster ongoing research new indications.Evidence suggests these benefits, studies indicating risk among people who [9][10][11][12]. explored GLP-1[3] liver health, including benefit treatment dysfunction associated fatty (MASLD) [13][14]. The anti-inflammatory neuroprotective properties being investigated, implications neurodegenerative conditions Alzheimer's [15][16][17]. Such raises possibility broader agonists, influence extends traditional management.As exciting advancements are, raise critical questions about society's preference pharmacological solutions lifestyle interventions diet exercise. mindset many practitioners, allure weight-loss medications indeed outweigh need changes, despite evidence that physical fundamental components sustainable Surveys internet worldwide indicated frank increase searches [18][19]. revealed more interested pharmaceutical loss than modifications. This trend is fueled relative ease accessibility medications, coupled perception can yield rapid, visible results (traditional social media statements "celebrities" add trend).Pharmaceutical companies responded demand pipeline drugs, based mechanisms agonists. focus pharmacotherapy, however, risks overshadowing essential role nonpharmacological chronic prevention management. It healthcare providers emphasize while play valuable plans, substitutes balanced diet, regular other modifications.While largely considered safe, usage drawn attention rare adverse events. Nonarteritic anterior ischemic optic neuropathy (NAION), idiopathic injury nerve head, marked sudden, painless vision eye swelling disc, reported association agonists' use, though such cases remain [20]. might trigger NAION yet fully understood, necessary determine whether causal [4] relationship exists. practice, experiencing visual disturbances therapy should evaluated promptly, consideration given discontinuing medication if link suspected.Pancreatitis known Although absolute low, pancreatitis severe even life-threatening. receptors expressed pancreas, researchers hypothesize pancreatic function ways could predispose certain individuals inflammation. Studies yielded mixed negative [21-23], there definitive linking higher incidence pancreatitis, remains listed effect.Other events, possibly linked analogs, include muscle mass loss, dermatological/hypersensitivity reactions, heart rate, left ventricular ejection fraction depressionThe emergence safety concerns reinforces importance individualized patient assessment before prescribing particularly those history disorders factors. Healthcare must engage thorough discussions patients, weighing benefits against ensuring understand signs symptoms events.The advent represents milestone obesity, presents challenge balancing drive innovation safety. landscape, devoid risks, detract from comprehensive, While offer much promise, underscore reality pharmacotherapy alone cannot root causes diseases. As we move forward, will crucial develop nuanced prescription drugs. Educating modification, well essential. needed clarify underlying events identify at [27].[5] transformed landscape management, offering extend control.However, reliance reflects societal de-emphasizing exercise managing although rare, serves reminder complexities drug careful selection monitoring. our pursuit advancements, innovative pharmacotherapies commitment safe responsible practice. providers, responsibility embrace tools modern medicine provides vigilant safeguarding health through informed, evidence-based promise undeniable, so caution judicious quest improve outcomes.

Language: Английский

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Advances in intrahepatic and extrahepatic vascular dysregulations in cirrhotic portal hypertension

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 31, 2025

Cirrhotic portal hypertension, the most prevalent and clinically significant complication of liver cirrhosis, manifests as elevated venous pressure is associated with severe complications. Although much research on mechanisms hypertension has focused fibrosis, less attention been given to role intrahepatic extrahepatic vascular dysfunction, particularly respect vasculature. While hepatic fibrosis in cirrhotic undeniable, underlying involving vasculature are highly complex. Sinusoidal capillarization endothelial dysfunction contribute increased resistance. Hemodynamic changes circulation, including splanchnic vasodilation hyperdynamic play a development hypertension. Additionally, therapeutic strategies targeting these diverse, improvement sinusoidal microcirculation, therapies stellate cells activation, pharmacological modulation systemic tone. Therefore, this review, we will discuss vascular-related treatment progress cirrhosis provide new theoretical basis practical guidance for clinical treatment.

Language: Английский

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Integrating 16S rDNA sequencing analysis and targeted metabolomics to explore the mechanism of Xiexin Tang in treating atherosclerosis mice induced by high-fat diet

Journal of Pharmaceutical and Biomedical Analysis, Journal Year: 2025, Volume and Issue: 259, P. 116760 - 116760

Published: Feb. 25, 2025

Language: Английский

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Unlocking the gut-liver axis: microbial contributions to the pathogenesis of metabolic-associated fatty liver disease

Frontiers in Microbiology, Journal Year: 2025, Volume and Issue: 16

Published: April 25, 2025

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex metabolic disorder characterized by hepatic lipid accumulation and subsequent inflammation. This condition closely linked to syndrome obesity, with its prevalence rising due sedentary lifestyles high-calorie diets. The pathogenesis of MAFLD involves multiple factors, including insulin resistance, lipotoxicity, oxidative stress, inflammatory responses. gut microbiota plays crucial role in development, dysbiosis contributing inflammation through various mechanisms, such as enhanced intestinal permeability the translocation bacterial products like lipopolysaccharide (LPS). Microbial metabolites, short-chain acids (SCFAs) bile acids, influence function immune responses, potential implications for progression. Specific microbiome signatures have been identified patients, offering diagnostic therapeutic targets. Moreover, gut-derived toxins, endotoxins, lipopolysaccharides, trimethylamine-N-oxide significantly damage inflammation, highlighting interplay between health. review comprehensively examines MAFLD, focusing on underlying pathogenic biomarkers, emerging microbiome-targeted strategies management.

Language: Английский

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Interplay of gut microbiota, glucagon-like peptide receptor agonists, and nutrition: New frontiers in metabolic dysfunction-associated steatotic liver disease therapy

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(43), P. 4682 - 4688

Published: Oct. 31, 2024

The gut-liver axis plays a crucial role in the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Key metabolites, including lipopolysaccharides, short-chain fatty acids (SCFAs), bile acids, beneficial gut bacteria such as Bifidobacterium Lactobacillus, are pivotal this process. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show promise managing MASLD by promoting weight loss, enhancing insulin secretion, improving health. They restore functionality, their effects amplified through dietary modifications microbiome-targeted therapies. Emerging research highlights interplay between GLP-1 RAs microbiota, indicating that microbiome significantly influences therapeutic outcomes. Metabolites produced bacteria, can stimulate glucagon-like (GLP-1) further Integrating interventions with RA treatment may enhance health modulating microbiota-SCFAs-GLP-1 pathway. Future is needed to understand personalized effects, prebiotics probiotics offering avenues for MASLD.

Language: Английский

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Editor-in-Chief articles of choice and comments from January to June 2024

World Journal of Gastroenterology, Journal Year: 2024, Volume and Issue: 30(34), P. 3875 - 3882

Published: Sept. 8, 2024

As the Editor-in-Chief of

Language: Английский

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Role of intestinal glucagon-like peptide-1 in hypoglycemia response impairment in type 1 diabetes

World Journal of Diabetes, Journal Year: 2024, Volume and Issue: 15(11), P. 2237 - 2241

Published: Oct. 16, 2024

This study critically examines the novel findings presented by Jin

Language: Английский

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