{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T00:58:37Z","timestamp":1793149117764,"version":"4.5.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolic dysfunction\u2010associated steatohepatitis (MASH) is a progressive liver disease with rising global prevalence, closely linked to type 2 diabetes. While several anti\u2010diabetic agents show promise, a comprehensive analysis comparing their efficacy on biopsy\u2010confirmed histological outcomes, including dose\u2010dependent effects and the mediating role of weight loss, remains unexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A frequentist random\u2010effects network meta\u2010analysis (NMA) was conducted to explore histological efficacy of anti\u2010diabetic agents in biopsy\u2010confirmed MASH without cirrhosis. The primary outcome was fibrosis improvement (\u22651 stage) without worsening steatohepatitis; the secondary outcome was MASH resolution without fibrosis worsening. Incretin\u2010based agents were dose\u2010stratified. Treatment ranking used surface\u2010under the cumulative\u2010ranking curve (SUCRA). Meta\u2010regression investigated the impact of percentage weight loss and baseline covariates on the proportion of individuals achieving histological end\u2010points.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Data from five RCTs (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20091667) were included. All active treatments, including Dapagliflozin 10 mg, Survodutide (2.4\u2009mg\/wk, 4.8\u20136 mg\/wk), Tirzepatide (5\u2009mg\/wk, 10\u201315 mg\/wk), and Semaglutide (0.7\u20131.4\u2009mg\/wk, 2.4 or 2.8 mg\/wk), improved fibrosis versus placebo (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u20090%). For MASH resolution, dose\u2010dependent effects led to significant heterogeneity (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200973%), with lower\u2010dose Semaglutide demonstrating no benefits and Dapagliflozin showing benefits in the F2\u2013F3 subgroup only on sensitivity analysis. Survodutide exhibited the highest ranking (SUCRA\u2009=\u20090.822\u20130.849), followed by Tirzepatide (SUCRA\u2009=\u20090.622\u20130.681) and higher\u2010dose Semaglutide (SUCRA\u2009=\u20090.327) for MASH resolution. Meta\u2010regression using data from 16 interventions, including placebo arms, showed that weight loss significantly explained heterogeneity in treatment effects on fibrosis improvement (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200954.26%) and MASH resolution (\n                      <jats:italic>R<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200978.16%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>SGLT2 inhibitor and incretin\u2010based agents improved fibrosis in MASH, with weight loss being a significant mediator. Targeting multiple incretin pathways, especially involving glucagon receptors, may offer greater MASH resolution. Dose\u2010dependent effects were more prominent for MASH resolution than fibrosis improvement, indicating potential weight\u2010loss\u2010independent anti\u2010fibrotic pathways.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.70187","type":"journal-article","created":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T04:31:12Z","timestamp":1759984272000},"page":"287-295","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Histological efficacy of anti\u2010diabetic agents in\n                    <scp>MASH<\/scp>\n                    and the mediating role of weight loss: A network meta\u2010analysis"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6656-8569","authenticated-orcid":false,"given":"Mainak","family":"Banerjee","sequence":"first","affiliation":[{"name":"Department of Endocrinology R N Tagore Hospital  Kolkata India"},{"name":"Department of Endocrinology 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