Safety and efficacy of semaglutide for non-alcoholic fatty liver disease: A meta-analysis of clinical outcomes

Safety and efficacy of semaglutide for non-alcoholic fatty liver disease: A meta-analysis of clinical outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Safety and efficacy of semaglutide for non-alcoholic fatty liver disease: A meta-analysis of clinical outcomes Muhammad Faique Hassan, Shamikha Cheema, Amna anwar, Muhammad Rafay-ur-Rehman, and 13 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9176897/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Non-alcoholic fatty liver disease (NAFLD) affects about 30.2% of the world and can progress from steatosis to non-alcoholic steatohepatitis (NASH) and fibrosis, contributing substantially to mortality and disability-adjusted life years. Because no FDA-approved pharmacologic therapy exists, sustained weight loss and exercise remain the principal effective options. Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown potential benefits; therefore, we conducted a PRISMA- and PROSPERO-aligned systematic review and meta-analysis to evaluate its efficacy and safety in adults with NAFLD/NASH. PubMed, Scopus, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception to January 29, 2026 for randomized controlled trials comparing oral or injectable semaglutide with placebo or another intervention; screening was performed in Rayyan. Efficacy outcomes included changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and complete NASH resolution when reported; safety outcomes included adverse events, particularly diarrhea, nausea, vomiting, and nasopharyngitis. Data were synthesized in R (v4.4.2) with p<0.05. Effect estimates were pooled as standardized mean differences for transaminases, using random-effects models to account for clinical diversity. NASH-resolution data were insufficient for meaningful pooled analysis. Six trials comprising 1,980 participants were included. Semaglutide significantly reduced ALT (SMD −0.74, 95% CI −1.11 to −0.36; p=0.0001) and AST (SMD −0.63, 95% CI −1.01 to −0.24; p=0.0014). However, semaglutide increased gastrointestinal adverse events, including diarrhea, nausea, and vomiting. Overall, semaglutide improves liver transaminases in adults with NAFLD/NASH but at the cost of higher rates of common adverse effects; larger and longer trials with standardized histologic and clinical endpoints are needed to define net benefit. Semaglutide NAFLD NASH meta-analysis GLP-1 agonist Full Text Additional Declarations No competing interests reported. Tables are available in the Supplementary Files section. Supplementary Files Tables.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-9176897","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":619287363,"identity":"c5a1786f-300a-4d15-b727-d3d9f10be0ce","order_by":0,"name":"Muhammad Faique Hassan","email":"","orcid":"","institution":"King Edward Medical University","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"Faique","lastName":"Hassan","suffix":""},{"id":619287364,"identity":"a093d32e-0727-42f7-b9d2-59629c91c9b7","order_by":1,"name":"Shamikha Cheema","email":"","orcid":"","institution":"King Edward Medical 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Because no FDA-approved pharmacologic therapy exists, sustained weight loss and exercise remain the principal effective options. Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown potential benefits; therefore, we conducted a PRISMA- and PROSPERO-aligned systematic review and meta-analysis to evaluate its efficacy and safety in adults with NAFLD/NASH. PubMed, Scopus, Embase, Cochrane CENTRAL, and ClinicalTrials.gov were searched from inception to January 29, 2026 for randomized controlled trials comparing oral or injectable semaglutide with placebo or another intervention; screening was performed in Rayyan. Efficacy outcomes included changes in alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and complete NASH resolution when reported; safety outcomes included adverse events, particularly diarrhea, nausea, vomiting, and nasopharyngitis. Data were synthesized in R (v4.4.2) with p\u003c0.05. 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