Steatotic Liver Disease: Pathophysiology and Emerging Pharmacotherapies

Pharmacological Reviews, Год журнала: 2024, Номер 76(3), С. 454 - 499

Опубликована: Янв. 30, 2024

Steatotic liver disease (SLD) displays a dynamic and complex phenotype. Consequently, the metabolic dysfunction-associated steatotic (MASLD)/metabolic steatohepatitis (MASH) therapeutic pipeline is expanding rapidly in multiple directions. In parallel, non-invasive tools for diagnosing monitoring responses to interventions are being studied, clinically feasible findings explored as primary outcomes interventional trials. The realization that distinct subgroups exist under umbrella of SLD should guide more precise personalized treatment recommendations facilitate advancements pharmacotherapeutics. This review summarizes recent updates pathophysiology-based nomenclature outlines both effective pharmacotherapeutics those MASLD/MASH, detailing their mode action current status phase 2 3 clinical Of extensive arsenal MASLD/MASH pipeline, several have been rejected, whereas other, mainly monotherapy options, shown only marginal benefits now tested part combination therapies, yet others still development monotherapies. Although successful drug candidate (or combinations) remains elusive, such approaches will ideally target MASH fibrosis while improving cardiometabolic risk factors. Due urgent need novel strategies potential availability safety tolerability data, repurposing existing approved drugs an appealing option. Finally, it essential highlight and, by extension, MASLD be recognized approached systemic affecting organs, with vigorous implementation interdisciplinary coordinated plans. Significance Statement SLD, including, among others, MASH, considered most prevalent chronic condition than one-fourth global population. aims provide information regarding pathophysiology, diagnosis, management line guidelines Collectively, hoped provided furthers understanding state direct implications stimulates additional research initiatives.

Язык: Английский

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Elective peri‐operative management of adults taking glucagon‐like peptide‐1 receptor agonists, glucose‐dependent insulinotropic peptide agonists and sodium‐glucose cotransporter‐2 inhibitors: a multidisciplinary consensus statement

Anaesthesia, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Summary Introduction Glucagon‐like peptide‐1 receptor agonists, dual glucose‐dependent insulinotropic peptide agonists and sodium‐glucose cotransporter‐2 inhibitors are used increasingly in patients receiving peri‐operative care. These drugs may be associated with risks of pulmonary aspiration or euglycaemic ketoacidosis. We produced a consensus statement for the management adults taking these drugs. Methods This multidisciplinary included surgeons, anaesthetists, physicians, pharmacists people lived experience relevant to guidelines. Following directed literature review, three‐round modified Delphi process was conducted generate ratify recommendations. Results Patients glucagon‐like should: continue before surgery; have full risk assessment stratification; receive techniques that mitigate before, during after sedation general anaesthesia. should omit them day procedure. All mitigation strategies discussed shared decision‐making approach. Discussion Until more evidence becomes available, this pragmatic, aims support improve safety period.

Язык: Английский

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The Effects of Sodium-Glucose Cotransporter 2-Inhibitors on Steatosis and Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease or Steatohepatitis and Type 2 Diabetes: A Systematic Review of Randomized Controlled Trials

Medicina, Год журнала: 2023, Номер 59(6), С. 1136 - 1136

Опубликована: Июнь 12, 2023

Type 2 Diabetes Mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are part of metabolic syndrome share multiple causal associations. Both conditions have an alarmingly increasing incidence lead to complications, which impact on a variety organs systems, such as the kidneys, eyes, nervous cardiovascular or may cause disruptions. Sodium-glucose cotransporter 2-inhibitors (SGLT2-i), antidiabetic class with well-established benefits, its members also been studied for their presumed effects steatosis fibrosis improvement in patients NAFLD steatohepatitis (NASH). The MEDLINE Cochrane databases were searched randomized controlled trials examining efficacy SGLT2-i treatment NAFLD/NASH T2DM. Of originally identified 179 articles, 21 articles included final data analysis. Dapagliflozin, empagliflozin, canagliflozin some most used agents proven treating by addressing/targeting different pathophysiological targets/mechanisms: insulin sensitivity improvement, weight loss, especially visceral fat glucotoxicity, lipotoxicity even chronic inflammation. Despite considerable variability study duration, sample size, diagnostic method, resulted improvements non-invasive markers This systematic review offers encouraging results that place at top therapeutic arsenal diagnosed T2DM NAFLD/NASH.

Язык: Английский

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New anti-diabetic agents for the treatment of non-alcoholic fatty liver disease: a systematic review and network meta-analysis of randomized controlled trials

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Июнь 27, 2023

This network meta-analysis aims to compare the efficacy and safety of new anti-diabetic medications for treatment non-alcoholic fatty liver disease (NAFLD).

Язык: Английский

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Glucometabolic outcomes of GLP-1 receptor agonist-based therapies in patients with type 2 diabetes: a systematic review and network meta-analysis

EClinicalMedicine, Год журнала: 2023, Номер 64, С. 102181 - 102181

Опубликована: Сен. 12, 2023

Innovative GLP-1 receptor agonist (GLP-1RA)-based treatment strategies-such as tirzepatide, GLP-1RA plus basal insulin fixed-ratio combinations [FRC], sodium glucose cotransporter-2 inhibitors [SGLT-2i] combinations, and high-dose GLP-1RA-have been listed among the most efficacious options for type 2 diabetes management. However, differences in their glucometabolic effects have not assessed dedicated head-to-head trials. In absence of such trials, we aimed to provide a useful comparison these strategies guide clinical practice.In this network meta-analysis, searched PubMed, MEDLINE, Web Science (from database inception June 24, 2023) randomised controlled studies, published English, that enrolled individuals with treated iGlarLixi, iDegLira, SGLT-2i combination, or (dulaglutide 3 mg 4.5 mg, semaglutide mg) compared placebo active comparators. Eligible studies reported change from baseline HbA1c an outcome, which was primary outcome analysis. Secondary outcomes were changes fasting post-prandial glucose, bodyweight, LDL-cholesterol, blood pressure risk hypoglycaemia. We bias through Cochrane Collaboration's tool (RoB2 tool), publication visual inspection funnel plots Egger's test, heterogeneity by comparing magnitude common between-study variance (τ2) each empirical distributions variances. This meta-analysis registered PROSPERO (CRD42022329878).40 trials included. Tirzepatide 15 ranked first terms reduction other GLP-1RA-based strategies, even those including (vs. iDegLira MD -0.40%, 95% CI [-0.66; -0.14], low certainty; vs. iGlarLixi -0.48%, [-0.75; -0.21], certainty), without increasing hypoglycaemia OR 0.35, [0.16; 0.79], high 0.31, [0.20; 0.48], certainty). also on weight lowering, (eg, -6.56 kg, [-7.38; -5.73], certainty) combination (MD -4.61 [-5.29; -3.93], Risk generally throughout while levels detected outcomes.Aiming support clinicians tailoring patients' needs, suggest hierarchy be devised considering best diabetes. Tirzepatide, followed FRC associated greater benefit than GLP-1RA.Fondazione per la Ricerca Biomedica "Saverio e Isabella Cianciola" Next Generation EU, context National Recovery Resilience Plan, Investment PE8-Project Age-It: Ageing Well Society.

Язык: Английский

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The Emerging Role of Glucagon-like Peptide-1 Receptor Agonists in the Management of Obesity-Related Heart Failure with Preserved Ejection Fraction: Benefits beyond What Scales Can Measure?

Biomedicines, Год журнала: 2024, Номер 12(9), С. 2112 - 2112

Опубликована: Сен. 16, 2024

Obesity is a significant predisposing factor for heart failure with preserved ejection fraction (HFpEF). Although substantial proportion of individuals HFpEF also have obesity, those obesity are under-represented in clinical trials failure. In turn, current guidelines provided limited recommendations the medical management this patient population. Both and diabetes induce pro-inflammatory state that can contribute to endothelial dysfunction coronary microvascular impairment, finally resulting HFpEF. Additionally, leads increased epicardial chest wall adiposity, which enhances ventricular interdependence. This condition further aggravated by plasma blood volume expansion excessive vasoconstriction, ultimately worsening Despite well-documented benefits GLP-1 receptor agonists subjects diabetes, or both, their role obesity-related remains unclear. light recently published literature, review aims investigate potential mechanisms synthesize available evidence regarding patients

Язык: Английский

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Effect of semaglutide versus other glucagon-like peptide-1 receptor agonists on cardio-metabolic risk factors in patients with type 2 diabetes: A systematic review and meta-analysis of head-to-head, phase 3, randomized controlled trials

Journal of Diabetes and its Complications, Год журнала: 2023, Номер 37(8), С. 108529 - 108529

Опубликована: Июнь 7, 2023

Язык: Английский

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Milestones in the journey towards addressing obesity; Past trials and triumphs, recent breakthroughs, and an exciting future in the era of emerging effective medical therapies and integration of effective medical therapies with metabolic surgery

Metabolism, Год журнала: 2023, Номер 148, С. 155689 - 155689

Опубликована: Сен. 7, 2023

Язык: Английский

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Precision Medicine in Fatty Liver Disease/Non-Alcoholic Fatty Liver Disease

Journal of Personalized Medicine, Год журнала: 2023, Номер 13(5), С. 830 - 830

Опубликована: Май 14, 2023

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic disease, and related to fatal non-fatal liver, metabolic, cardiovascular complications. Its non-invasive diagnosis effective treatment remain an unmet clinical need. NAFLD a heterogeneous that commonly present in context of metabolic syndrome obesity, but not uncommonly, may also be without abnormalities subjects with normal body mass index. Therefore, more specific pathophysiology-based subcategorization (FLD) needed better understand, diagnose, treat patients FLD. A precision medicine approach for FLD expected improve patient care, decrease long-term outcomes, develop better-targeted, treatments. We herein based on our recently proposed subcategorization, which includes metabolic-associated (MAFLD) (i.e., obesity-associated (OAFLD), sarcopenia-associated (SAFLD, lipodystrophy-associated (LAFLD)), genetics-associated (GAFLD), multiple/unknown causes (XAFLD), combined (CAFLD) as well advanced stage fibrotic (FAFLD) end-stage (ESFLD) subcategories. These other advances, whole, are enable only improved quality life, considerable reduction healthcare system costs associated FLD, along options treatments near future.

Язык: Английский

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Effect of Semaglutide on Subclinical Atherosclerosis and Cardiometabolic Compensation: A Real-World Study in Patients with Type 2 Diabetes

Biomedicines, Год журнала: 2023, Номер 11(5), С. 1362 - 1362

Опубликована: Май 4, 2023

Semaglutide is a recently approved glucagon-like peptide-1 receptor agonist. Several trials reported the protective effect of injectable semaglutide on cardiovascular (CV) risk by reducing major adverse events in type 2 diabetes patients. Strong preclinical evidence supports CV benefits through an atherosclerosis. However, scant available about mechanisms clinical practice.A retrospective observational study was conducted among consecutive patients treated with Italy between November 2019 and January 2021 when drug first country. The primary aims were assessment carotid intima-media thickness (cIMT) hemoglobin A1c (HbA1c) levels. secondary evaluation anthropometric, glycemic, hepatic parameters plasma lipids, including triglyceride/high-density lipoprotein ratio as indirect marker atherogenic small, dense low-density particles.Injectable reduced HbA1c cIMT. An improvement factors reported. Moreover, correlation analyses, we found that fibrosis steatosis indices hepatic, glycemic parameters, well unrelated to variations cIMT HbA1c.Our findings suggest atherosclerosis key mechanism. Considering favorable effects lipoproteins indices, our results support pleiotropic beyond control.

Язык: Английский

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