The pleiotropic effects of glucagon-like peptide-1 receptor agonists in patients with metabolic dysfunction-associated steatohepatitis: a review for gastroenterologists

Expert Opinion on Investigational Drugs, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Glucagon-like peptide-1 receptor agonists (GLP-1RAs), and dual GLP-1/glucose-dependent insulinotropic peptide (GIP) or glucagon have emerged as promising agents to treat metabolic dysfunction-associated steatotic liver disease (MASLD)/metabolic steatohepatitis (MASH). Although the beneficial effects of GLP-1RAs on glycemic control weight are well-established, clinicians may be unfamiliar with other potential benefits this class. We examined pleiotropic how they relate gastroenterologists for MASLD/MASH treatment. Our narrative review English articles included four (subcutaneous semaglutide, liraglutide, dulaglutide, efpeglenatide), a GLP-1/GIP agonist (tirzepatide), GLP-1/glucagon (survodutide), MASLD/MASH, related disorders, clinical management, treatment outcomes landscape. In Phase I - III trials, associated clinically relevant hepatic improvements including MASH resolution, fat reduction, preventing worsening fibrosis. Effects cardiometabolic parameters align type 2 diabetes/obesity data, comprising substantial in glycemic, weight, cardiovascular outcomes. Promising data also suggest common comorbidities, obstructive sleep apnea, polycystic ovary syndrome, chronic kidney disease, heart failure preserved ejection fraction.GLP-1RAs represent valuable pharmacotherapeutic option managing individuals comorbid conditions.

Language: Английский

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Budget impact of resmetirom for the treatment of adults with non-cirrhotic non-alcoholic steatohepatitis (NASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis)

Journal of Medical Economics, Journal Year: 2024, Volume and Issue: 27(1), P. 1108 - 1118

Published: Aug. 19, 2024

Aims This study assessed the budget impact of resmetirom as a treatment for adults with non-cirrhotic non-alcoholic steatohepatitis (NASH) moderate-to-advanced liver fibrosis and estimated total costs hypothetical private payer in United States.

Language: Английский

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Survival and Cost-Effectiveness of Bariatric Surgery Among Patients With Obesity and Cirrhosis

JAMA Surgery, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

Obesity and steatotic liver disease are associated with excess morbidity mortality from cardiovascular, pulmonary, metabolic, hepatic causes. Bariatric surgery has demonstrated long-term benefits in terms of weight loss rates, but barriers to its utilization persist. To evaluate the impact bariatric on outcomes cost-effectiveness among patients obesity, focusing those cirrhosis. This economic evaluation was a retrospective cohort study including US veterans older than 18 years body mass index (BMI) higher 35 or BMI 30 more 1 major metabolic comorbidity. These were referred structured lifestyle modification program (MOVE!), subset proceeded surgery, sleeve gastrectomy (SG) Roux-en-Y gastric bypass (RYGB) 2008 2020. Risk set matching used match cases 1:5 nonsurgical controls. Data analyzed September 2023. (SG RYGB) intervention (MOVE!). The primary incremental ratio (ICER) SG RYGB vs MOVE! over 10 years. Secondary included overall survival, quality-adjusted achieved. final 4301 SG, 1906 RYGB, 31 055 participants, whom 64, 8, 354, respectively, had median (IQR) age 52 (44-59) years; there 25 581 male (68.7%) 11 681 female (31.3%). Compared MOVE!, longer observed survival (9.67 9.46 overall; 9.09 8.23 cirrhosis). ICER $132 207 for $159 027 cohort, $18 679 $44 704 cirrhosis cohorts. cost-effective at willingness-to-pay threshold $100 000 per life-year improved expected cost-effective. findings support expanded use appropriately selected patients, cirrhosis, improve reduce health care costs.

Language: Английский

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Clinical Insights on Resmetirom

Journal of Clinical Gastroenterology, Journal Year: 2025, Volume and Issue: 59(5), P. 412 - 419

Published: Feb. 13, 2025

The recent conditional approval by the Food and Drug Administration of resmetirom for treating metabolic dysfunction-associated steatohepatitis (MASH) with significant or advanced fibrosis represents a pivotal milestone in history steatotic liver disease (MASLD) treatment. As first liver-directed pharmacological therapy option MASLD, offers novel approach that specifically targets pathology, marking transformative step forward managing this widespread challenging condition. For initiating resmetirom, biopsy is not required. Consequently, accurately excluding patients less severe histology cirrhosis using noninvasive tests (NITs) essential. In addition, monitoring response should be conducted NITs. Given approval, our current clinical understanding primarily informed phase 3 trials. long-term effects drug evaluated further studies encouraging use eligible patients. This review highlights key aspects use, including identifying target population, therapeutic response, determining appropriate discontinuation criteria, strategies to prevent unnecessary treatment interruptions.

Language: Английский

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Estimating the clinical and healthcare burden of metabolic dysfunction-associated steatohepatitis in England: a retrospective cohort study using routinely collected healthcare data from 2011 to 2020

BMJ Open, Journal Year: 2025, Volume and Issue: 15(4), P. e095761 - e095761

Published: April 1, 2025

Objective To characterise patients with metabolic dysfunction-associated steatohepatitis (MASH) in England and to estimate its associated healthcare resource use (HCRU) costs, both overall by progression status comorbidities. Design This was a retrospective observational study of adults MASH-coded primary and/or secondary care recorded diagnosis (2011–2020). The analysis used data from the Clinical Practice Research Datalink linked Hospital Episode Statistics death registrations. Annualised all-cause MASH-related (ie, coded as MASH, end-stage liver disease or major adverse cardiovascular event) HCRU costs were calculated for incident MASH. Subgroup analyses conducted type 2 diabetes, overweight/obesity, cirrhosis. Comparative cost between those progressed MASH who did not progress. Results A total 2696 included (mean follow-up: 4 years). Incidence estimated at 4.7 per 100 000 person-years increased among key Patients had diabetes greater than (eg, mean 1.8 vs 1.0 inpatient admissions £2227 £1151 per-patient per-year). Some compensated (8.6%) decompensated cirrhosis (6.5%) during study. substantially higher 2.4 1.1 £3620 £1290 Conclusion are have cardiometabolic comorbidities progress advanced stages. Therefore, efforts detect cases early prevent could reduce burden.

Language: Английский

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Estimation of the Eligible Population For Resmetirom Among Adults in the United States for Treatment of Non-Cirrhotic NASH with Moderate-to-Advanced Liver Fibrosis

Advances in Therapy, Journal Year: 2024, Volume and Issue: 41(11), P. 4172 - 4190

Published: Sept. 18, 2024

As of March 2024, resmetirom is the first and only therapy approved in United States (US) for treatment adults with non-cirrhotic nonalcoholic steatohepatitis (NASH) moderate-to-advanced liver fibrosis (MALF) consistent stages F2/F3 fibrosis. Estimates diagnosed, treatment-eligible NASH population are poorly understood due to diagnostic variability. This study provides a contemporary estimate size US population.

Language: Английский

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Progression from Non-alcoholic Steatohepatitis to Advanced Liver Diseases and Mortality Among Medicare Patients

Advances in Therapy, Journal Year: 2024, Volume and Issue: 41(11), P. 4335 - 4355

Published: Sept. 24, 2024

Non-alcoholic steatohepatitis (NASH) may progress to more advanced liver disease. This study aimed characterize NASH progression and mortality in the Medicare population.

Language: Английский

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Artificial Intelligence in Identifying Patients With Undiagnosed Nonalcoholic Steatohepatitis

Journal of health economics and outcomes research, Journal Year: 2024, Volume and Issue: 11(2)

Published: Sept. 25, 2024

Background: Although increasing in prevalence, nonalcoholic steatohepatitis (NASH) is often undiagnosed clinical practice. Objective: This study identified patients the Veterans Affairs (VA) health system who likely had NASH using a machine learning algorithm. Methods: From VA data set of 25 million adult enrollees, population was divided into NASH-positive, non-NASH, and at-risk cohorts. We performed claims analysis To build our model, randomly an 80% training subset 20% testing tested trained cross-validation technique. In addition to baseline gradient-boosted classification tree, naïve Bayes, random forest model were created compared receiver operator characteristics, area under curve, accuracy. The best performing retrained on full applied calculate performance metrics. Results: total, 4 223 443 met inclusion criteria, whom 4903 positive for 35 528 non-NASH patients. remainder patient cohort, which 514 997 (12%) as have NASH. Age, obesity, abnormal liver function tests top determinants assigning probability. Conclusions: Utilization predict allows wider recognition, timely intervention, targeted treatments improve or mitigate disease progression could be used initial screening tool.

Language: Английский

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Costs associated with nonalcoholic steatohepatitis disease progression in Medicare patients: a retrospective cohort study

Journal of Comparative Effectiveness Research, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Aim: Non-alcoholic steatohepatitis (NASH), or metabolic dysfunction-associated (MASH), is a severe form of non-alcoholic fatty liver disease (NAFLD) (MASLD), that may progress to advanced disease. Costs associated with progression are not well characterized. This study sought quantify costs and healthcare resource utilization (HRU) NASH progression. Methods: Patients were included if diagnosed (ICD-10: K75.81) in 100% Medicare claims data (2015–2021) who ≥66 years at index (diagnosis), continuously enrolled Parts A, B D for ≥12 months prior 6 following (unless death) had no evidence other causes Patient-time was categorized into five severity states: non-cirrhotic NASH, compensated cirrhosis (CC), decompensated (DCC), hepatocellular carcinoma (HCC) transplant (LT). Annualized HRU calculated during the periods overall stratified by occurrence timing Results: In 14,806 unique patients (n = 12,990 NASH; 1899 CC; 997 DCC; 209 HCC; 140 LT), mean age follow-up 72.2 2.8 years, respectively. Average annualized increased from baseline diagnosis, generally scaling severity: $16,231 $27,044; $25,122 $57,705; $40,613 $181,036; $36,549 $165,121 $35,626 $108,918 LT; Non-cirrhotic CC higher spending (1.6x 1.7x CC) than non-progressors (both p < 0.001), 6.1-times odds an inpatient stay 2.6 3.6-times be top 20% spenders, respectively, relative 0.001). progressing within year 1.4, 1.6, 1.7 2.2-times more 2, 3, 4 5 progressors' costs, 1.3, 1.8, 2.0 CC. Conclusion: high increase states. Slower lower suggesting potential benefit therapies delay prevent

Language: Английский

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