{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T19:59:13Z","timestamp":1794340753922,"version":"4.9.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Non-alcoholic fatty liver disease (NAFLD) is common, can progress to cirrhosis and hepatic decompensation, and has no approved medical therapy in Canada.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We conducted a systematic review on whether glucagon-like peptide-1 receptor agonists (GLP-1RA) improve non-alcoholic steatohepatitis (NASH) compared to standard care in NAFLD.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We searched Medline Ovid, EMBASE(Elsevier), Cochrane CENTRAL, Clinical Trials.gov, and the World Health Organization International Clinical Trials Registry Platform in November 2023 for randomized controlled trials. Inclusion criteria included patients \u226513 years with NAFLD receiving GLP-1RA for \u22656 months compared to standard care\/placebo. Cochrane risk-of-bias 2.0 tool was used for each outcome. After screening results in duplicate, we performed meta-analysis and reported odds ratios (OR) for dichotomous and mean difference of change score for continuous outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Six studies with 478 patients met inclusion criteria; 3 studies reported on the primary endpoint resolution of NASH. GLP-1RA likely leads to resolution of NASH (OR 4.45 (95% CI 1.92, 10.3)) and reduction in liver steatosis on imaging (\u20135.09% (95% CI \u22127.49, \u22122.69), but little to no reduction in liver stiffness on imaging (mean difference \u20130.17 kPa (95% CI \u22120.34, 0)).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Interpretation<\/jats:title>\n                  <jats:p>Treatment with GLP-1RA in NAFLD patients for \u22656 months can probably lead to improvement in NASH on liver biopsy and reduce liver steatosis on imaging. Whether improvements in steatosis on biopsy or imaging results in clinically significant outcomes need to be elucidated as the effects of GLP-1RA on liver fibrosis are unclear; larger ongoing trials may provide more definitive answers.<\/jats:p>\n                  <jats:p>Protocol Registration: PROSPERO\u2013CRD42023472186.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jcag\/gwae057","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T20:46:57Z","timestamp":1738183617000},"page":"47-57","source":"Crossref","is-referenced-by-count":13,"title":["Effects of GLP-1 receptor agonist therapy on resolution of steatohepatitis in non-alcoholic fatty liver disease: a systematic review and meta-analysis"],"prefix":"10.1093","volume":"8","author":[{"given":"Kathryn J","family":"Potter","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Cumming School of Medicine, University of Calgary , Calgary, AB, T2N 4Z5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jackie","family":"Phinney","sequence":"additional","affiliation":[{"name":"Dalhousie University, Dalhousie Medicine New Brunswick , Saint John, NB, E2L 4L5 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tasha","family":"Kulai","sequence":"additional","affiliation":[{"name":"Division of Digestive Care and Endoscopy, Dalhousie University , Halifax, NS, B3H 2Y9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3125-5044","authenticated-orcid":false,"given":"Vicki","family":"Munro","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Dalhousie University , Halifax, NS, B3H 2Y9 ,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"issue":"2","key":"2025042603014847600_CIT0001","doi-asserted-by":"publisher","first-page":"E429","DOI":"10.9778\/cmajo.20190212","article-title":"Burden of nonalcoholic fatty liver disease in Canada, 2019\u20132030: a modelling study","volume":"8","author":"Swain","year":"2020","journal-title":"CMAJ Open"},{"issue":"10","key":"2025042603014847600_CIT0002","doi-asserted-by":"publisher","first-page":"e13067","DOI":"10.1111\/ijpo.13067","article-title":"Review of paediatric obesity and non-alcoholic fatty liver disease\u2014a focus on emerging non-pharmacologic treatment strategies","volume":"18","author":"Piester","year":"2023","journal-title":"Pediatr Obes"},{"issue":"5","key":"2025042603014847600_CIT0003","doi-asserted-by":"publisher","first-page":"1797","DOI":"10.1097\/HEP.0000000000000323","article-title":"AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease","volume":"77","author":"Rinella","year":"2023","journal-title":"Hepatology."},{"issue":"3","key":"2025042603014847600_CIT0004","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.jhep.2024.04.031","article-title":"EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD)","volume":"81","author":"European Association for the Study of the Liver (EASL). European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO); European Association for the Study of the Liver (EASL)","year":"2024","journal-title":"J Hepatol."},{"issue":"3","key":"2025042603014847600_CIT0005","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1016\/j.jhep.2023.04.025","article-title":"An individual patient data meta-analysis to determine cut-offs for and confounders of NAFLD-fibrosis staging with magnetic resonance elastography","volume":"79","author":"Liang","year":"2023","journal-title":"J Hepatol."},{"issue":"March","key":"2025042603014847600_CIT0006","doi-asserted-by":"publisher","first-page":"101351","DOI":"10.1016\/j.molmet.2021.101351","article-title":"GLP-1 physiology informs the pharmacotherapy of obesity","volume":"57","author":"Drucker","year":"2022","journal-title":"Mol Metab"},{"issue":"10","key":"2025042603014847600_CIT0007","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1007\/s00125-023-05956-x","article-title":"Incretin hormones and type 2 diabetes","volume":"66","author":"Nauck","year":"2023","journal-title":"Diabetologia."},{"issue":"8","key":"2025042603014847600_CIT0008","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1111\/dom.15077","article-title":"New insights into the treatment of obesity","volume":"25","author":"Bl\u00fcher","year":"2023","journal-title":"Diabetes Obes Metab."},{"issue":"6","key":"2025042603014847600_CIT0009","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1016\/j.jhep.2023.07.033","article-title":"Incretins (GLP-1 receptor agonists and dual\/triple agonists) and the liver","volume":"79","author":"Newsome","year":"2023","journal-title":"J Hepatol."},{"issue":"6","key":"2025042603014847600_CIT0010","doi-asserted-by":"publisher","first-page":"4544","DOI":"10.3390\/cimb45060288","article-title":"The role of GLP1-RAs in direct modulation of lipid metabolism in hepatic tissue as determined using in vitro models of NAFLD","volume":"45","author":"Petrovic","year":"2023","journal-title":"Curr Issues Mol Biol."},{"issue":"8","key":"2025042603014847600_CIT0011","doi-asserted-by":"publisher","first-page":"e0289616","DOI":"10.1371\/journal.pone.0289616","article-title":"The effects of GLP-1 receptor agonists on visceral fat and liver ectopic fat in an adult population with or without diabetes and nonalcoholic fatty liver disease: a systematic review and meta-analysis","volume":"18","author":"Liao","year":"2023","journal-title":"PLoS One."},{"issue":"June","key":"2025042603014847600_CIT0012","doi-asserted-by":"publisher","first-page":"1170881","DOI":"10.3389\/fendo.2023.1170881","article-title":"Comparing the effectiveness of long-term use of daily and weekly glucagon-like peptide-1 receptor agonists treatments in patients with nonalcoholic fatty liver disease and type 2 diabetes mellitus: a network meta-analysis","volume":"14","author":"Yuan","year":"2023","journal-title":"Front Endocrinol."},{"issue":"1","key":"2025042603014847600_CIT0013","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1111\/jgh.13026","article-title":"Incretin-based therapies for the treatment of non-alcoholic fatty liver disease: A systematic review and meta-analysis","volume":"31","author":"Carbone","year":"2016","journal-title":"J Gastroenterol Hepatol."},{"issue":"8","key":"2025042603014847600_CIT0014","doi-asserted-by":"publisher","first-page":"627","DOI":"10.17235\/reed.2020.6392\/2019","article-title":"The efficacy of glucagon-like peptide 1 receptor agonists in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trials","volume":"112","author":"Fan","year":"2020","journal-title":"Rev Esp Enferm Dig."},{"issue":"3","key":"2025042603014847600_CIT0015","doi-asserted-by":"publisher","first-page":"101568","DOI":"10.1016\/j.clinre.2020.10.012","article-title":"Liraglutide in patients with non-alcoholic fatty liver disease: a systematic review and meta-analysis of randomized controlled trials","volume":"45","author":"Kalogirou","year":"2021","journal-title":"Clin Res Hepatol Gastroenterol"},{"issue":"June","key":"2025042603014847600_CIT0016","doi-asserted-by":"publisher","first-page":"1182037","DOI":"10.3389\/fendo.2023.1182037","article-title":"New anti-diabetic agents for the treatment of non-alcoholic fatty liver disease: a systematic review and network meta-analysis of randomized controlled trials","volume":"14","author":"Kongmalai","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"Nov","key":"2025042603014847600_CIT0017","doi-asserted-by":"publisher","first-page":"8936865","DOI":"10.1155\/2021\/8936865","article-title":"GLP-1 receptor agonist effects on lipid and liver profiles in patients with nonalcoholic fatty liver disease: Systematic review and meta-analysis","volume":"2021","author":"Rezaei","year":"2021","journal-title":"Can J Gastroenterol Hepatol"},{"issue":"3","key":"2025042603014847600_CIT0018","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/j.clinre.2016.11.009","article-title":"Efficacy and safety of glucagon-like peptide-1 receptor agonists in non-alcoholic fatty liver disease: a systematic review and meta-analysis","volume":"41","author":"Dong","year":"2017","journal-title":"Clin Res Hepatol Gastroenterol."},{"issue":"Feb","key":"2025042603014847600_CIT0019","doi-asserted-by":"publisher","first-page":"622589","DOI":"10.3389\/fendo.2020.622589","article-title":"Comparison of the efficacy of glucagon-like peptide-1 receptor agonists in patients with metabolic associated fatty liver disease: updated systematic review and meta-analysis","volume":"11","author":"Dai","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"6","key":"2025042603014847600_CIT0020","doi-asserted-by":"publisher","first-page":"e32892","DOI":"10.1097\/MD.0000000000032892","article-title":"Liraglutide on type 2 diabetes mellitus with nonalcoholic fatty liver disease: a systematic review and meta-analysis of 16 RCTs","volume":"102","author":"Zhao","year":"2023","journal-title":"Medicine (Baltim)."},{"issue":"April","key":"2025042603014847600_CIT0021","doi-asserted-by":"publisher","first-page":"609110","DOI":"10.3389\/fendo.2021.609110","article-title":"Glucagon-like peptide-1 receptor agonists for non-alcoholic fatty liver disease in type 2 diabetes: a meta-analysis","volume":"12","author":"Wong","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"Oct","key":"2025042603014847600_CIT0022","doi-asserted-by":"publisher","first-page":"769069","DOI":"10.3389\/fendo.2021.769069","article-title":"Efficacy and safety of GLP-1 receptor agonists in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease: a systematic review and meta-analysis","volume":"12","author":"Zhu","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"37","key":"2025042603014847600_CIT0023","doi-asserted-by":"publisher","first-page":"5327","DOI":"10.3748\/wjg.v29.i37.5327","article-title":"Efficacy and safety of semaglutide in non-alcoholic fatty liver disease","volume":"29","author":"Zhu","year":"2023","journal-title":"World J Gastroenterol."},{"key":"2025042603014847600_CIT0024","author":"European Medicines Agency"},{"key":"2025042603014847600_CIT0025","author":"Food and Drug Administration, CDER"},{"issue":"Mar","key":"2025042603014847600_CIT0026","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"issue":"1","key":"2025042603014847600_CIT0027","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s13643-020-01542-z","article-title":"PRISMA-S: an extension to the PRISMA statement for reporting literature searches in systematic reviews","volume":"10","author":"Rethlefsen","year":"2021","journal-title":"Syst Rev"},{"key":"2025042603014847600_CIT0028","article-title":"Chapter 4: Searching for and selecting studies","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions version 6.4 (updated October 2023)","author":"Lefebvre","year":"2023"},{"issue":"July","key":"2025042603014847600_CIT0029","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.jclinepi.2016.01.021","article-title":"PRESS peer review of electronic search strategies: 2015 guideline statement","volume":"75","author":"McGowan","year":"2016","journal-title":"J Clin Epidemiol."},{"key":"2025042603014847600_CIT0030","author":"Covidence Systematic Review Software, Veritas Health Innovation, Melbourne, Australia"},{"issue":"Suppl","key":"2025042603014847600_CIT0031","doi-asserted-by":"publisher","first-page":"S17","DOI":"10.3350\/cmh.2022.0367","article-title":"MAFLD: How is it different from NAFLD","volume":"29","author":"Gofton","year":"2023","journal-title":"Clin Mol Hepatol"},{"issue":"Aug","key":"2025042603014847600_CIT0032","doi-asserted-by":"publisher","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: a revised tool for","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"2025042603014847600_CIT0033","article-title":"Chapter 8: Assessing risk of bias in a randomized trial","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions Version 6.4 (Updated August 2023)","author":"Higgins","year":"2023"},{"key":"2025042603014847600_CIT0034","author":"Sch\u00fcnemann","year":"2013"},{"key":"2025042603014847600_CIT0035","volume-title":"McMaster University and Evidence Prime","author":"GRADEpro Guideline Development Tool [Software]","year":"2023"},{"issue":"6","key":"2025042603014847600_CIT0036","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/S2468-1253(23)00068-7","article-title":"Semaglutide 2\u00b74 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial","volume":"8","author":"Loomba","year":"2023","journal-title":"Lancet Gastroenterol Hepatol."},{"issue":"10019","key":"2025042603014847600_CIT0037","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/S0140-6736(15)00803-X","article-title":"Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis (LEAN): a multicentre, double-blind, randomised, placebo-controlled phase 2 study","volume":"387","author":"Armstrong","year":"2016","journal-title":"Lancet."},{"issue":"9","key":"2025042603014847600_CIT0038","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1111\/apt.16608","article-title":"Randomised clinical trial: semaglutide versus placebo reduced liver steatosis but not liver stiffness in subjects with non-alcoholic fatty liver disease assessed by magnetic resonance imaging","volume":"54","author":"Flint","year":"2021","journal-title":"Alimentary Pharmacol Therap."},{"issue":"5","key":"2025042603014847600_CIT0039","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1111\/liv.14065","article-title":"Randomized trial comparing effects of weight loss by liraglutide with lifestyle modification in non-alcoholic fatty liver disease","volume":"39","author":"Khoo","year":"2019","journal-title":"Liver Int."},{"issue":"Dec","key":"2025042603014847600_CIT0040","doi-asserted-by":"publisher","first-page":"108487","DOI":"10.1016\/j.diabres.2020.108487","article-title":"Liraglutide or insulin glargine treatments improves hepatic fat in obese patients with type 2 diabetes and nonalcoholic fatty liver disease in twenty-six weeks: a randomized placebo-controlled trial","volume":"170","author":"Guo","year":"2020","journal-title":"Diabetes Res Clin Pract."},{"issue":"12","key":"2025042603014847600_CIT0041","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1056\/NEJMoa2028395","article-title":"A placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis","volume":"384","author":"Newsome","year":"2021","journal-title":"N Engl J Med."},{"issue":"11","key":"2025042603014847600_CIT0042","doi-asserted-by":"publisher","first-page":"2274","DOI":"10.1016\/j.cgh.2020.08.061","article-title":"Change in MRI-PDFF and histologic response in patients with nonalcoholic steatohepatitis: a systematic review and meta-analysis","volume":"19","author":"Stine","year":"2021","journal-title":"Clin Gastroenterol Hepatol."},{"key":"2025042603014847600_CIT0043","author":"Guerci"},{"key":"2025042603014847600_CIT0044"},{"key":"2025042603014847600_CIT0045"},{"key":"2025042603014847600_CIT0046","author":"Loomba"},{"issue":"1","key":"2025042603014847600_CIT0047","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.jceh.2021.08.002","article-title":"Magnetic resonance elastography for the clinical risk assessment of fibrosis, cirrhosis, and portal hypertension in patients with NAFLD","volume":"12","author":"Natarajan","year":"2022","journal-title":"J Clin Exp Hepatol"},{"issue":"10","key":"2025042603014847600_CIT0048","doi-asserted-by":"publisher","first-page":"e1912565","DOI":"10.1001\/jamanetworkopen.2019.12565","article-title":"Association of histologic disease activity with progression of nonalcoholic fatty liver disease","volume":"2","author":"Kleiner","year":"2019","journal-title":"JAMA Netw Open"},{"issue":"2","key":"2025042603014847600_CIT0049","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1111\/apt.12352","article-title":"Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis","volume":"38","author":"Hoofnagle","year":"2013","journal-title":"Aliment Pharmacol Ther."},{"issue":"10","key":"2025042603014847600_CIT0050","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1016\/j.cgh.2014.03.026","article-title":"Serum alanine aminotransferase as a biomarker of treatment response in nonalcoholic steatohepatitis","volume":"12","author":"Loomba","year":"2014","journal-title":"Clin Gastroenterol Hepatol."}],"container-title":["Journal of the Canadian Association of Gastroenterology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcag\/article-pdf\/8\/2\/47\/61685432\/gwae057.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcag\/article-pdf\/8\/2\/47\/61685432\/gwae057.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T07:01:55Z","timestamp":1745650915000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcag\/article\/8\/2\/47\/7989366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,29]]},"references-count":50,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,4,11]]}},"URL":"https:\/\/doi.org\/10.1093\/jcag\/gwae057","relation":{},"ISSN":["2515-2084","2515-2092"],"issn-type":[{"value":"2515-2084","type":"print"},{"value":"2515-2092","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,4]]},"published":{"date-parts":[[2025,1,29]]}}}